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Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer

Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT01347866
Collaborator
(none)
105
Enrollment
18
Locations
2
Arms
50
Actual Duration (Months)
5.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

After the fourth protocol amendment two study arms are evaluated in this clinical protocol:

PD-0325901 (oral MEK inhibitor) plus PF-05212384 (intravenous PI3K/mTOR inhibitor) and PF-05212384 plus irinotecan. The study will assess safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer. Once the maximum tolerated doses are identified, further assessment of these combinations will be done in patients with previously treated metastatic colorectal or pancreatic cancer for the PF-05212384 plus irinotecan arm and in patients with ovarian cancer or KRAS mutated non small cell lung cancer for the combination of PF-05212384 plus PD-0325901.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The study was prematurely discontinued as a result of an internal portfolio review on April 1, 2015. The decision to terminate was not due to any safety or efficacy data.

Study Design

Study Type:
Interventional
Actual Enrollment :
105 participants
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A Multi-arm Phase 1 Dose Escalation Study Of The Safety, Pharmacokinetics, And Pharmacodynamics Of The Dual Pi3k/Mtor Inhibitors Pf-04691502 And Pf-05212384 In Combination With Experimental Or Approved Anticancer Agents In Patients With Advanced Cancer
Actual Study Start Date :
Oct 1, 2011
Actual Primary Completion Date :
Dec 1, 2015
Actual Study Completion Date :
Dec 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm D: PF-05212384 + PD-0325901

Drug: PF-05212384
PF-05212384 intravenous infusion weekly starting at 110 mg.

Drug: PD-0325901
PD-0325901 Oral twice daily (BID) dosing 2 mg BID 3 weeks on 1 week off
Experimental: Arm C: PF-05212384 + irinotecan

Drug: PF-05212384
PF-05212384 intravenous infusion weekly starting at 95 mg.

Drug: irinotecan
Irinotecan by intravenous infusion at 180 mg/m2 every two weeks (Q x 2 week)

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle (28 Days) [Baseline up to 28 days]

    DLT was defined as any of the following hematologic or non-hematologic events which were attributable to the combination study drug and occurring in the first 28-day cycle: 1) Grade 4 neutropenia lasting greater than (>)7 days; 2) Febrile neutropenia (defined as neutropenia greater than or equal to [≥]Grade 3 and a body temperature ≥38.5°C); 3) Grade ≥3 neutropenic infection; 4) Grade 3 thrombocytopenia with bleeding; 5) Grade 4 thrombocytopenia; 6) Grade ≥3 toxicities; 7) Persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses during the first cycle; 8) Persistent, intolerable toxicities which resulted in delay of start of Cycle 2 by more than 2 weeks of scheduled day; 9) Persistent Grade 3 QTc prolongation (QTc >500 msec) after correction of any reversible causes.

Secondary Outcome Measures

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  2. Number of Participants With Treatment-Emergent AEs (TEAEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade [Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded by the NCI CTCAE (Version 4.0).

  3. Number of Participants With Laboratory Test Abnormalities (Hematology) [Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 hematological test abnormalities. Hematological tests included platelet count, hemoglobin, and white blood cell (WBC) count with 5- part differential.

  4. Number of Participants With Laboratory Test Abnormalities (Coagulation) [Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 coagulation test abnormalities. Coagulation tests included partial thromboplastin time (PTT) and prothrombin time (PT) international normalized ratio (INR).

  5. Number of Participants With Laboratory Test Abnormalities (Chemistry) [Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 chemistry test abnormalities. Chemistry tests included aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]), serum creatinine, total bilirubin, direct/indirect bilirubin, alkaline phosphatase, chloride, uric acid, phosphorus, calcium, magnesium, potassium, sodium, blood urea nitrogen (BUN) or urea, total protein, albumin, glucose, and insulin.

  6. Number of Participants With Laboratory Test Abnormalities (Urinalysis) [Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 urinalysis test abnormalities for urine protein.

  7. Number of Participants With Vital Signs Values Meeting Prespecified Criteria [Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Number of participants with vital signs values meeting prespecified criteria. Criteria defined as: 1) absolute systolic blood pressue (SBP) less than or equal to (<=) 100 millimeter of mercury (mmHg); 2) absolute SBP greater than or equal to (>=) 160 mmHg, 3) SBP maximum increase of >=20 mmHg from baseline; 4) SBP maximum increase of >=40 mmHg from baseline; 5) SBP maximum increase of >=60 mmHg from baseline; 6) absolute diastolic blood pressure (DBP) <=60 mmHg; 7) absolute DBP >=100 mmHg; 8) DBP maximum increase of >=10 mmHg from baseline; 9) DBP maximum increase of >=20 mmHg from baseline; 10) DBP maximum increase of >=30 mmHg from baseline; 11) absolute heart rate (HR) <50 beats per minute (bpm); 12) absolute HR >120 bpm.

  8. Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C [Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  9. Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D [Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  10. Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D [Cycle 0 Day -1 and Cycle 1 Day 1: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.]

  11. Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A [Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.]

  12. Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  13. Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B [Cycle 0 Day -7 at 0 hours (pre-dose) and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6 8 and 24 hours post-dose.]

  14. Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C [Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  15. Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D [Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  16. Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D [Cycle 0 Day -1 and Cycle 1 Day 1: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.]

  17. Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A [Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.]

  18. Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  19. Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B [Cycle 0 Day -7 at 0 hours (pre-dose) and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6 8 and 24 hours post-dose.]

  20. Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C [Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  21. Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D [Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  22. Terminal Elimination Half Life (t½) for PD-0325901 on Cycle 0 Day -7 for Arm A [Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.]

  23. Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  24. Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  25. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C [Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  26. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D [Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  27. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PD-0325901 on Cycle 0 Day -7 for Arm A [Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.]

  28. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm A [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  29. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm B [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  30. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C [Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  31. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D [Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.]

  32. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PD-0325901 on Cycle 0 Day -7 for Arm A [Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.]

  33. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm A [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  34. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm B [Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.]

  35. Number of Participants With Increase From Baseline in QT Interval [Baseline, Cycle 1 Day 2 for Arms C and D, Cycle 1 Day 15 for Arm D, and Cycle 1 Day 16 for Arm C, Day 2 in Arm C and Day 1 in Arm D for subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett's Formula (QTcB) and Fridericia's Formula (QTcF) .

  36. Number of Participants With Maximum Post-dose QT Interval Corrected [Baseline, Cycle 1 Day 2 for Arms C and D, Cycle 1 Day 15 for Arm D, and Cycle 1 Day 16 for Arm C, Day 2 in Arm C and Day 1 in Arm D for subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)]

    Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett's Formula (QTcB) and Fridericia's Formula (QTcF).

  37. Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until progression of disease was documented.]

    CR was defined as the disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest diameters of the targeted lesions.

  38. Progression-Free Survival (PFS) (Stage 2) [Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until progression of disease was documented.]

    Progression-free survival (PFS) was the time from first dose to date of first documentation of progression or death due to any cause.

  39. Ratio to Baseline in Serum Glucose Level at End of Treatment for Arm B, Arm C, and Arm D [Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)]

  40. Ratio to Baseline in Serum Insulin Level at End of Treatment for Arm B, Arm C, and Arm D [Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)]

  41. Ratio to Baseline in Serum Glucose Level at Cycle 2 Day 16 for Arm A [Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)]

  42. Ratio to Baseline in Serum Insulin Level at Cycle 2 Day 16 for Arm A [Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)]

  43. Number of Participants With Expression of Genes Relating to Phosphatidylinositol 3 Kinase (PI3K), Mitogen Activated Protein Kinase (MAPK) and/or Wingless-Type Mouse Mammary Tumor Virus Integration Site Family Member (Wnt) Pathway Signaling [Baseline and Cycle 1 Day 23.]

    Number of participants with expression of genes relating to PI3K, MAPK and/or Wnt pathway signaling (kirsten rat sarcoma 2 viral oncogene homolog [KRAS] and PTEN protein). Biopsies were obtained at baseline and Cycle 1 Day 23. Biomarker evaluation was performed on these biopsies.

  44. Duration of Response (Stage 2) [Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until until progression of disease was documented.]

    Duration of response was to be calculated for participants with an objective response. Duration of PR or CR was the time from start date (date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR: disappearance of a target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Histological or cytological diagnosis of advanced/metastatic solid tumor for which there is no currently clinically effective treatment.

  • All tumor types for patients enrolled in Stage 1 of Arm C.

  • For patients enrolled in Stage 2 of Arm C, advanced colorectal cancer (both KRAS mutated and KRAS wild type), which has progressed on irinotecan-based regimens, and pancreatic ductal adenocarcinoma after progression on first line treatment for metastatic/advanced disease.

  • For patients enrolled in Stage 1 of Arm D, tumors with KRAS or BRAF mutation (archived or fresh biopsy). Patients with tumors harboring other mutations that activate the MAPK pathway may be enrolled upon agreement with the Sponsor.

  • For patients enrolled in Stage 2 of Arm D, ovarian cancer which has progressed on prior platinum containing regimen or KRAS mutated non small cell lung cancer which has progressed on one prior regimen.

  • Patients with colorectal cancer enrolled to both Arms must:

  1. have received at least 6 weeks of irinotecan-based therapy (either as single agent or in combination with cytotoxic drugs or in combination with targeted therapies) as the last prior treatment

  2. have progressed on or within 1 month of completing this irinotecan-based regimen

  • All patients must provide an archived or fresh tumor sample.

  • For a subset of patients fresh tumor biopsies are mandatory:

  1. All patients with CRC enrolled to Stage 2 of Arm C must provide a fresh tumor biopsy at baseline. A subset of patients (10 or more) with at least 5 evaluable patients with CRC KRAS wild type must also provide tumor biopsy during treatment.

  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1

  • Adequate Bone Marrow, Renal, Cardiac, and Liver Function

Exclusion Criteria:

  • -Patients with known active brain metastases

  • -Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 4 weeks of the start of the study treatment (6 weeks for mitomycin C or nitrosoureas).

  • -Any surgery (not including minor procedures such as lymph node biopsy, needle biopsy, and/or placement of port-a-cath) within 4 weeks of start of the study treatment; or not fully recovered from any side effects of previous procedures.

  • -In Arm D only: Patients with glaucoma, intraocular pressure > 21 mmHg, history of retinal vein occlusions, ocular ischemia or any other clinically significant abnormality in the ophthalmologic exam which would make the patient inappropriate for entry into this study

  • -For patients enrolling in Stage 2 prior therapy with an agent that is known or proposed to be active by action on PI3K and/or mTOR.

  • -Prior high dose chemotherapy requiring hematopoietic stem cell transplantation within 12 months of study treatment start.

  • -Known impaired pulmonary function or demonstrated to be impaired by Pulmonary Function Test (PFT) for patients who present with clinical suggestion of impairment.

  • -Uncontrolled or significant cardiovascular disease

  • -Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors

    • Current or anticipated need for food or drugs that are known potent CYP3A4 inducers

Contacts and Locations

Locations

Site City State Country Postal Code
1 Ronald Reagan UCLA Medical Center Los Angeles California United States 90095-6984
2 Ronald Reagan UCLA Medical Center Los Angeles California United States 90095
3 UCLA Medical Center Los Angeles California United States 90095
4 UCLA Oncology Center Los Angeles California United States 90095
5 Santa Monica - UCLA Medical Center and Orthopaedic Hospital Santa Monica California United States 90404
6 UCLA Santa Monica Hematology Oncology Santa Monica California United States 90404
7 Anschutz Cancer Pavilion Aurora Colorado United States 80045
8 University of Colorado Denver (CTRC) Aurora Colorado United States 80045
9 University of Colorado Hospital Anschutz Inpatient Pavilion Aurora Colorado United States 80045
10 University of Colorado Hospital Aurora Colorado United States 80045
11 Medical University of South Carolina, Hollings Cancer Center Charleston South Carolina United States 29425
12 Medical University of South Carolina Charleston South Carolina United States 29425
13 MUSC, Investigational Drug Services Charleston South Carolina United States 29425
14 MUSC Health East Cooper Mount Pleasant South Carolina United States 29464
15 MUSC Specialty Care-North North Charleston South Carolina United States 29406
16 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
17 Ospedale San Raffaele Milano Italy 20132
18 Hospital General Vall d'Hebron Barcelona Spain 08035

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01347866
Other Study ID Numbers:
  • B1271002
  • 2011-001671-39
First Posted:
May 4, 2011
Last Update Posted:
Oct 29, 2018
Last Verified:
Feb 1, 2018
Keywords provided by Pfizer
Advanced metastatic cancer (solid tumors)
PI3K
mTOR
MEK
Additional relevant MeSH terms:
Neoplasms
Irinotecan
Gedatolisib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail In Arms A and B, 7 and 14 participants were screed and received study treatment, respectively. In Arm C, 45 participants were screened and 44 received study treatment. In Arm D, 39 participants were screened and 37 received study treatment. There was no Stage 2 for Arm D, the study was terminated before enrolling patients to Stage 2 for Arm D.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Period Title: Overall Study
STARTED 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
NOT COMPLETED 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2

Baseline Characteristics

Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+ PD-0325901: Arm D1B (Stage 1)) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1) Total
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Total of all reporting groups
Overall Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2 102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
58.8
(8.7)
54.0
(0.0)
49.0
(0.0)
53.6
(14.1)
59.1
(12.9)
67.0
(3.6)
60.8
(7.2)
63.3
(14.5)
56.7
(12.4)
63.3
(5.9)
43.3
(9.1)
64.0
(8.9)
55.7
(10.0)
57.9
(12.9)
61.3
(14.2)
60.0
(11.8)
54.5
(9.2)
58.5
(11.8)
Sex: Female, Male (Count of Participants)
Female
3
60%
0
0%
0
0%
5
71.4%
2
28.6%
2
66.7%
2
33.3%
2
50%
13
41.9%
3
42.9%
1
33.3%
2
50%
3
42.9%
2
28.6%
0
0%
2
50%
2
100%
44
43.1%
Male
2
40%
1
100%
1
100%
2
28.6%
5
71.4%
1
33.3%
4
66.7%
2
50%
18
58.1%
4
57.1%
2
66.7%
2
50%
4
57.1%
5
71.4%
3
100%
2
50%
0
0%
58
56.9%

Outcome Measures

1. Primary Outcome
Title Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle (28 Days)
Description DLT was defined as any of the following hematologic or non-hematologic events which were attributable to the combination study drug and occurring in the first 28-day cycle: 1) Grade 4 neutropenia lasting greater than (>)7 days; 2) Febrile neutropenia (defined as neutropenia greater than or equal to [≥]Grade 3 and a body temperature ≥38.5°C); 3) Grade ≥3 neutropenic infection; 4) Grade 3 thrombocytopenia with bleeding; 5) Grade 4 thrombocytopenia; 6) Grade ≥3 toxicities; 7) Persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses during the first cycle; 8) Persistent, intolerable toxicities which resulted in delay of start of Cycle 2 by more than 2 weeks of scheduled day; 9) Persistent Grade 3 QTc prolongation (QTc >500 msec) after correction of any reversible causes.
Time Frame Baseline up to 28 days

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment and who did not have a major pre-specified treatment deviation in the first cycle of treatment in Stage 1.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 5 3 6 4 7 3 4 7 7 3 3 1
Number [percentage of participants]
40.0
800%
0
0%
100
10000%
14.3
204.3%
40.0
571.4%
0
0%
0
0%
50.0
1250%
14.3
46.1%
0
0%
0
0%
14.3
357.5%
14.3
204.3%
0
0%
0
0%
0
0%
2. Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
AEs
5
100%
1
100%
1
100%
7
100%
7
100%
3
100%
6
100%
4
100%
31
100%
7
100%
3
100%
4
100%
7
100%
7
100%
3
100%
4
100%
2
100%
SAEs
2
40%
1
100%
1
100%
2
28.6%
5
71.4%
0
0%
0
0%
2
50%
5
16.1%
3
42.9%
1
33.3%
2
50%
4
57.1%
1
14.3%
0
0%
1
25%
0
0%
3. Secondary Outcome
Title Number of Participants With Treatment-Emergent AEs (TEAEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade
Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded by the NCI CTCAE (Version 4.0).
Time Frame Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Any AEs, Grade 1
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
2
33.3%
0
0%
7
22.6%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
25%
1
50%
Any AEs, Grade 2
2
40%
0
0%
0
0%
5
71.4%
2
28.6%
3
100%
4
66.7%
1
25%
10
32.3%
2
28.6%
2
66.7%
2
50%
3
42.9%
2
28.6%
1
33.3%
3
75%
0
0%
Any AEs, Grade 3
2
40%
1
100%
1
100%
2
28.6%
5
71.4%
0
0%
0
0%
2
50%
10
32.3%
3
42.9%
1
33.3%
1
25%
2
28.6%
4
57.1%
2
66.7%
0
0%
1
50%
Any AEs, Grade 4
1
20%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
25%
4
12.9%
1
14.3%
0
0%
1
25%
0
0%
1
14.3%
0
0%
0
0%
0
0%
Any AEs, Grade 5
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
2
28.6%
0
0%
0
0%
0
0%
0
0%
Any AEs, Missing or Unknown
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Any AEs, Total
5
100%
1
100%
1
100%
7
100%
7
100%
3
100%
6
100%
4
100%
31
100%
7
100%
3
100%
4
100%
7
100%
7
100%
3
100%
4
100%
2
100%
4. Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Hematology)
Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 hematological test abnormalities. Hematological tests included platelet count, hemoglobin, and white blood cell (WBC) count with 5- part differential.
Time Frame Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Anemia
5
1
1
5
6
3
6
4
31
6
3
3
7
5
3
3
2
Hemoglobin Increased
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Lymphocyte Count Increased
0
0
0
0
0
0
0
0
1
1
1
0
1
1
0
0
0
Lymphopenia
5
1
1
7
7
3
5
3
22
5
1
1
6
6
3
1
1
Absolute Neutrophils
1
0
0
3
3
0
2
3
18
0
0
0
0
1
0
1
1
Platelets
3
0
0
4
2
1
1
3
10
0
0
2
1
3
1
1
1
White Blood Cells
3
0
0
5
3
3
3
4
22
1
0
0
2
0
1
1
1
5. Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Coagulation)
Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 coagulation test abnormalities. Coagulation tests included partial thromboplastin time (PTT) and prothrombin time (PT) international normalized ratio (INR).
Time Frame Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment. N=number of evaluable participants for each parameter.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
PTT (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
2
0
0
2
5
2
0
2
21
2
3
2
2
5
0
3
2
PT INR (N=5,1,1,7,7,3,6,4,30,7,3,4,7,7,3,4,2)
1
0
1
2
5
0
1
2
13
0
1
1
3
2
1
2
0
6. Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Chemistry)
Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 chemistry test abnormalities. Chemistry tests included aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]), serum creatinine, total bilirubin, direct/indirect bilirubin, alkaline phosphatase, chloride, uric acid, phosphorus, calcium, magnesium, potassium, sodium, blood urea nitrogen (BUN) or urea, total protein, albumin, glucose, and insulin.
Time Frame Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
ALT
3
0
1
2
3
0
3
3
13
3
1
2
5
4
3
1
2
Alkaline phosphatase
3
1
1
5
6
1
3
2
22
4
3
4
6
6
3
4
2
AST
4
0
1
3
5
0
3
2
16
4
2
3
5
6
3
3
2
Total bilirubin
0
0
1
2
2
0
1
1
3
2
0
2
1
4
1
1
0
creatinine
5
1
0
5
6
3
5
3
21
5
2
3
5
2
3
4
2
hypercalcemia
0
0
0
0
0
0
0
0
1
0
1
0
0
0
0
1
0
hyperglycemia
5
1
1
6
6
3
5
3
25
5
2
3
7
7
2
4
2
hyperkalemia
1
0
0
2
1
0
1
1
2
1
1
0
1
2
0
0
0
hypermagnesemia
0
0
0
0
0
0
0
1
2
2
0
0
2
1
0
0
1
hypernatremia
1
0
0
0
1
0
0
1
2
0
0
0
0
0
0
1
0
hypoalbuminemia
3
1
1
3
6
0
3
3
18
3
2
4
6
6
3
2
2
hypocalcemia
3
0
1
4
4
1
0
4
13
2
2
3
1
4
1
1
2
hypoglycemia
0
0
0
0
1
0
1
0
3
1
1
1
0
2
1
0
0
hypokalemia
2
1
1
2
3
0
0
3
14
3
1
2
3
4
0
2
1
hypomagnesemia
2
0
0
3
4
2
2
1
10
2
1
2
0
2
1
2
1
hyponatremia
1
1
0
4
3
0
1
3
14
2
2
2
4
3
1
1
1
hypophosphatemia
4
1
0
2
5
0
2
1
8
1
1
1
3
3
0
1
0
7. Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Urinalysis)
Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 urinalysis test abnormalities for urine protein.
Time Frame Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment. Number of participants analyzed=number of evaluable participants for each laboratory parameter.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 6 7 3 4 2
Number [participant]
2
1
1
6
4
1
3
1
15
3
0
2
5
4
1
2
0
8. Secondary Outcome
Title Number of Participants With Vital Signs Values Meeting Prespecified Criteria
Description Number of participants with vital signs values meeting prespecified criteria. Criteria defined as: 1) absolute systolic blood pressue (SBP) less than or equal to (<=) 100 millimeter of mercury (mmHg); 2) absolute SBP greater than or equal to (>=) 160 mmHg, 3) SBP maximum increase of >=20 mmHg from baseline; 4) SBP maximum increase of >=40 mmHg from baseline; 5) SBP maximum increase of >=60 mmHg from baseline; 6) absolute diastolic blood pressure (DBP) <=60 mmHg; 7) absolute DBP >=100 mmHg; 8) DBP maximum increase of >=10 mmHg from baseline; 9) DBP maximum increase of >=20 mmHg from baseline; 10) DBP maximum increase of >=30 mmHg from baseline; 11) absolute heart rate (HR) <50 beats per minute (bpm); 12) absolute HR >120 bpm.
Time Frame Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment. N=number of participants evaluated against criteria.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Criterion 1 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
1
20%
0
0%
0
0%
4
57.1%
3
42.9%
0
0%
1
16.7%
1
25%
9
29%
2
28.6%
2
66.7%
3
75%
1
14.3%
2
28.6%
0
0%
1
25%
2
100%
Criterion 2 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
1
20%
0
0%
0
0%
0
0%
0
0%
1
33.3%
0
0%
0
0%
4
12.9%
2
28.6%
0
0%
0
0%
3
42.9%
0
0%
0
0%
1
25%
0
0%
Criterion 3 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)
1
20%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
25%
7
22.6%
3
42.9%
1
33.3%
1
25%
3
42.9%
0
0%
0
0%
2
50%
0
0%
Criterion 4 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
3.2%
2
28.6%
0
0%
0
0%
1
14.3%
0
0%
0
0%
1
25%
0
0%
Criterion 5 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
3.2%
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
1
25%
0
0%
Criterion 6 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
0
0%
0
0%
0
0%
3
42.9%
3
42.9%
1
33.3%
2
33.3%
1
25%
14
45.2%
1
14.3%
2
66.7%
1
25%
2
28.6%
3
42.9%
1
33.3%
1
25%
1
50%
Criterion 7 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
0
0%
3
9.7%
1
14.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Criterion 8 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)
3
60%
0
0%
1
100%
4
57.1%
1
14.3%
1
33.3%
0
0%
3
75%
10
32.3%
1
14.3%
1
33.3%
2
50%
3
42.9%
0
0%
1
33.3%
3
75%
1
50%
Criterion 9 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)
0
0%
0
0%
1
100%
1
14.3%
0
0%
1
33.3%
0
0%
0
0%
1
3.2%
1
14.3%
1
33.3%
0
0%
1
14.3%
0
0%
0
0%
0
0%
0
0%
Criterion10 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Criterion11 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
Criterion12 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)
0
0%
1
100%
0
0%
0
0%
0
0%
0
0%
1
16.7%
0
0%
0
0%
1
14.3%
0
0%
0
0%
1
14.3%
0
0%
0
0%
0
0%
0
0%
9. Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C
Description
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 2 6 4 30
Cycle 1 Day 2 (N=2, 6, 4, 30)
NA
(NA)
3404
(82)
4759
(25)
5221
(61)
Cycle 1 Day 16 (N=3, 6, 4, 28)
2201
(16)
2814
(50)
4656
(32)
5728
(56)
10. Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Description
Time Frame Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 7 3 4 7 6 3 4 2
Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)
3625
(62)
5937
(32)
11170
(16)
8476
(32)
8586
(36)
6279
(70)
7239
(39)
NA
(NA)
Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)
8621
(18)
6153
(34)
12440
(32)
8717
(50)
8913
(54)
9280
(NA)
7989
(45)
15400
(NA)
11. Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D
Description
Time Frame Cycle 0 Day -1 and Cycle 1 Day 1: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 7 3 3 7 7 3 3 2
Cycle 0 Day -1 (N=7, 3, 3, 7, 7, 3, 3, 2)
85.28
(27)
63.80
(14)
87.99
(51)
180.6
(28)
191.9
(44)
115.8
(70)
231.3
(69)
NA
(NA)
Cycle 1 Day 1 (N=5, 3, 3, 6, 6, 3, 4, 2)
91.69
(31)
74.23
(43)
64.99
(56)
138.7
(23)
183.6
(29)
114.6
(50)
211.9
(44)
NA
(NA)
12. Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Description
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Cycle 0 Day -7 (N=5, 1, 1)
304.9
(49)
280
(NA)
101
(NA)
Cycle 1 Day 12 (N=4, 1, 1)
341.9
(21)
690
(NA)
182
(NA)
13. Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Cycle 0 Day -7 (N=5, 1, 1)
38.02
(28)
59.8
(NA)
48.7
(NA)
Cycle 1 Day 12 (N=4, 1, 1)
52.02
(13)
21.2
(NA)
64.7
(NA)
14. Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose) and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6 8 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Measure Participants 7 7
Cycle 0 Day -7 (N=7, 7)
41.44
(8.1201)
68.41
(31.818)
Cycle 1 Day 12 (N=7, 5)
46.81
(19.381)
87.30
(37.647)
15. Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C
Description
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 2 6 4 30
Cycle 1 Day 2 (N=2, 6, 4, 30)
1.30
1.02
0.992
0.500
Cycle 1 Day 16 (N=3, 6, 4, 28)
1.00
0.992
0.734
0.525
16. Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Description
Time Frame Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 7 3 4 7 6 3 4 2
Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)
0.500
0.500
0.500
0.500
0.509
1.00
0.500
0.500
Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)
0.500
0.500
0.500
0.509
0.517
0.667
0.500
0.500
17. Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D
Description
Time Frame Cycle 0 Day -1 and Cycle 1 Day 1: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 7 3 3 7 7 3 3 2
Cycle 0 Day -1 (N=7, 3, 3, 7, 7, 3, 3, 2)
1.00
2.00
1.03
1.97
1.07
1.00
2.00
2.50
Cycle 1 Day 1 (N=5, 3, 3, 6, 6, 3, 4, 2)
1.00
2.00
1.00
2.00
1.00
2.00
1.50
1.00
18. Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Description
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Cycle 0 Day -7 (N=5, 1, 1)
1.00
2.00
1.92
Cycle 1 Day 12 (N=4, 1, 1)
1.00
1.00
4.00
19. Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Cycle 0 Day -7 (N=5, 1, 1)
1.00
1.00
1.90
Cycle 1 Day 12 (N=4, 1, 1)
2.00
0.00
2.00
20. Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose) and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6 8 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Measure Participants 7 7
Cycle 0 Day -7 (N=7, 7)
2
1.07
Cycle 1 Day 12 (N=7, 5)
2
2.03
21. Secondary Outcome
Title Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C
Description
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 1 5 3 25
Cycle 1 Day 2 (N=1, 5, 3, 25)
24.5
(NA)
32.14
(1.3334)
29.23
(7.1066)
32.16
(4.5154)
Cycle 1 Day 16 (N=1, 5, 3, 20)
33.3
(NA)
37.98
(5.5603)
34.50
(8.4256)
35.10
(3.3067)
22. Secondary Outcome
Title Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Description
Time Frame Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 3 3 6 6 3 4 2
Cycle 0 Day -14 (N=5, 3, 3, 6, 6, 3, 4, 2)
24.62
(3.2306)
27.37
(6.4748)
30.77
(6.4933)
25.85
(4.1530)
29.35
(5.5121)
29.63
(3.7072)
27.05
(4.6651)
NA
(NA)
Cycle 1 Day 15 (N=3, 3, 4, 6, 3, 1, 3, 1)
35.90
(4.8816)
39.30
(10.678)
41.25
(6.2303)
34.43
(8.5383)
40.20
(5.8643)
37.0
(NA)
33.30
(0.96437)
37.0
(NA)
23. Secondary Outcome
Title Terminal Elimination Half Life (t½) for PD-0325901 on Cycle 0 Day -7 for Arm A
Description
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Mean (Standard Deviation) [hr]
13.92
(4.2260)
18.3
(NA)
25.7
(NA)
24. Secondary Outcome
Title Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Cycle 0 Day -7 (N=5, 1, 1)
9.374
(1.3243)
12.4
(NA)
11.5
(NA)
Cycle 1 Day 12 (N=4, 0, 0)
8.968
(1.5366)
NA
(NA)
NA
(NA)
25. Secondary Outcome
Title Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Measure Participants 6 7
Cycle 0 Day -7 (N=6, 7)
13.13
(2.2879)
13.06
(2.6589)
Cycle 1 Day 12 (N=3, 1)
8.597
(1.2726)
8.97
(NA)
26. Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C
Description
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 3 6 4 31
Cycle 1 Day 2 (N=2, 6, 4, 30)
NA
(NA)
7487
(41)
10530
(44)
9485
(43)
Cycle 1 Day 16 (N=3, 6, 4, 28)
8819
(71)
8243
(25)
11170
(53)
10890
(38)
27. Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Description
Time Frame Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 7 3 4 7 7 3 4 2
Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)
7627
(46)
10250
(21)
14850
(31)
12590
(27)
14280
(24)
13840
(47)
9619
(22)
NA
(NA)
Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)
12070
(36)
12130
(1)
19970
(25)
13390
(21)
21170
(36)
15200
(NA)
12610
(25)
20800
(NA)
28. Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PD-0325901 on Cycle 0 Day -7 for Arm A
Description
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
1479
(23)
2030
(NA)
941
(NA)
29. Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm A
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
474.5
(29)
933
(NA)
688
(NA)
30. Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm B
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Measure Participants 7 7
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
588.4
(49)
1001
(35)
31. Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C
Description
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 3 6 4 31
Cycle 1 Day 2 (N=1, 5, 3, 25)
7540
(NA)
7968
(41)
9277
(48)
10070
(42)
Cycle 1 Day 16 (N=1, 5, 3, 20)
5870
(NA)
8627
(26)
9174
(17)
10610
(37)
32. Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Description
Time Frame Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 7 3 4 7 7 3 4 2
Cycle 0 Day -14 (N=5, 3, 3, 6, 6, 3, 4, 2)
6353
(40)
10460
(20)
14880
(39)
12600
(29)
14620
(23)
14230
(46)
9766
(22)
NA
(NA)
Cycle 1 Day 15 (N=3, 3, 4, 6, 3, 1, 3, 1)
10430
(33)
12460
(2)
20440
(26)
13770
(20)
23730
(39)
15500
(NA)
13320
(27)
21300
(NA)
33. Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PD-0325901 on Cycle 0 Day -7 for Arm A
Description
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
1599
(26)
2140
(NA)
1060
(NA)
34. Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm A
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
523.9
(21)
950
(NA)
697
(NA)
35. Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm B
Description
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.

Outcome Measure Data

Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Measure Participants 6 7
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
705.0
(41)
1028
(36)
36. Secondary Outcome
Title Number of Participants With Increase From Baseline in QT Interval
Description Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett's Formula (QTcB) and Fridericia's Formula (QTcF) .
Time Frame Baseline, Cycle 1 Day 2 for Arms C and D, Cycle 1 Day 15 for Arm D, and Cycle 1 Day 16 for Arm C, Day 2 in Arm C and Day 1 in Arm D for subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All participants enrolled in the study having at least one ECG assessment after receiving study drug for the respective arm.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 30 7 3 3 7 5 3 4 2
Maximum QTcB Interval Increase <30msec
4
80%
0
0%
1
100%
7
100%
7
100%
2
66.7%
5
83.3%
4
100%
28
90.3%
7
100%
2
66.7%
2
50%
6
85.7%
4
57.1%
3
100%
3
75%
2
100%
MaximumQTcB Interval Increase >=30to<60msec
1
20%
1
100%
0
0%
0
0%
0
0%
1
33.3%
1
16.7%
0
0%
2
6.5%
0
0%
1
33.3%
1
25%
1
14.3%
1
14.3%
0
0%
1
25%
0
0%
Maximum QTcB Interval Increase >=60 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Maximum QTcF Interval Increase <30 msec
5
100%
0
0%
1
100%
7
100%
5
71.4%
2
66.7%
5
83.3%
3
75%
24
77.4%
6
85.7%
3
100%
2
50%
6
85.7%
5
71.4%
3
100%
4
100%
2
100%
MaximumQTcF Interval Increase >=30 to<60msec
0
0%
1
100%
0
0%
0
0%
2
28.6%
1
33.3%
1
16.7%
1
25%
6
19.4%
1
14.3%
0
0%
1
25%
1
14.3%
0
0%
0
0%
0
0%
0
0%
Maximum QTcF Interval Increase >=60 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
37. Secondary Outcome
Title Number of Participants With Maximum Post-dose QT Interval Corrected
Description Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett's Formula (QTcB) and Fridericia's Formula (QTcF).
Time Frame Baseline, Cycle 1 Day 2 for Arms C and D, Cycle 1 Day 15 for Arm D, and Cycle 1 Day 16 for Arm C, Day 2 in Arm C and Day 1 in Arm D for subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)

Outcome Measure Data

Analysis Population Description
All participants enrolled in the study having at least one ECG assessment after receiving study drug for the respective arm.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Maximum QTcB Interval <450 msec
2
40%
0
0%
1
100%
4
57.1%
3
42.9%
2
66.7%
4
66.7%
1
25%
22
71%
2
28.6%
3
100%
3
75%
2
28.6%
4
57.1%
3
100%
2
50%
1
50%
Maximum QTcB Interval 450 to <=480 msec
3
60%
0
0%
0
0%
3
42.9%
4
57.1%
1
33.3%
2
33.3%
3
75%
5
16.1%
5
71.4%
0
0%
1
25%
5
71.4%
1
14.3%
0
0%
1
25%
0
0%
Maximum QTcB Interval >480 to <=500 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
2
6.5%
0
0%
0
0%
0
0%
0
0%
2
28.6%
0
0%
0
0%
1
50%
Maximum QTcB Interval >500 msec
0
0%
1
100%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
2
6.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
25%
0
0%
Maximum QTcF Interval <450 msec
4
80%
0
0%
1
100%
7
100%
3
42.9%
3
100%
6
100%
2
50%
24
77.4%
6
85.7%
3
100%
4
100%
6
85.7%
5
71.4%
3
100%
2
50%
1
50%
Maximum QTcF Interval 450 to <=480 msec
1
20%
0
0%
0
0%
0
0%
4
57.1%
0
0%
0
0%
2
50%
5
16.1%
1
14.3%
0
0%
0
0%
1
14.3%
2
28.6%
0
0%
2
50%
0
0%
Maximum QTcF Interval >480 to <=500 msec
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
3.2%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
50%
Maximum QTcF Interval >500 msec
0
0%
1
100%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
3.2%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
38. Secondary Outcome
Title Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Description CR was defined as the disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest diameters of the targeted lesions.
Time Frame Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until progression of disease was documented.

Outcome Measure Data

Analysis Population Description
All participants who started treatment on the assigned arm and had an adequate baseline tumor assessment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 7 6 3 6 4 30 7 3 3 7 7 3 4 2
Number [percentage of participants]
0
0%
0
0%
0
0%
0
0%
0
0%
33.3
1110%
0
0%
0
0%
3.3
10.6%
0
0%
33.3
1110%
0
0%
28.6
408.6%
14.3
204.3%
0
0%
0
0%
0
0%
39. Secondary Outcome
Title Progression-Free Survival (PFS) (Stage 2)
Description Progression-free survival (PFS) was the time from first dose to date of first documentation of progression or death due to any cause.
Time Frame Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until progression of disease was documented.

Outcome Measure Data

Analysis Population Description
All participants who started treatment on the assigned arm and had an adequate baseline tumor assessment.
Arm/Group Title PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 30
Median (95% Confidence Interval) [months]
2.8
40. Secondary Outcome
Title Ratio to Baseline in Serum Glucose Level at End of Treatment for Arm B, Arm C, and Arm D
Description
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 5 2 5 3 25 5 3 2 6 5 3 4 1
Mean (Standard Deviation) [ratio]
0.974
(0.0864)
1.015
(0.1935)
NA
(NA)
1.011
(0.1165)
NA
(NA)
1.111
(0.2895)
1.212
(0.3284)
NA
(NA)
NA
(NA)
0.966
(0.1904)
1.13
(0.3886)
NA
(NA)
NA
(NA)
NA
(NA)
41. Secondary Outcome
Title Ratio to Baseline in Serum Insulin Level at End of Treatment for Arm B, Arm C, and Arm D
Description
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 4 6 2 5 3 22 4 3 1 5 4 3 4 1
Mean (Standard Deviation) [ratio]
NA
(NA)
1.628
(1.888)
NA
(NA)
2.178
(2.3194)
NA
(NA)
1.699
(2.0031)
NA
(NA)
NA
(NA)
NA
(NA)
2.233
(2.3617)
NA
(NA)
NA
(NA)
NA
(NA)
NA
(NA)
42. Secondary Outcome
Title Ratio to Baseline in Serum Glucose Level at Cycle 2 Day 16 for Arm A
Description
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 0
Mean (Standard Deviation) [ratio]
0.965
(0.2697)
NA
(NA)
43. Secondary Outcome
Title Ratio to Baseline in Serum Insulin Level at Cycle 2 Day 16 for Arm A
Description
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 0
Mean (Standard Deviation) [ratio]
0.652
(0.3622)
NA
(NA)
44. Secondary Outcome
Title Number of Participants With Expression of Genes Relating to Phosphatidylinositol 3 Kinase (PI3K), Mitogen Activated Protein Kinase (MAPK) and/or Wingless-Type Mouse Mammary Tumor Virus Integration Site Family Member (Wnt) Pathway Signaling
Description Number of participants with expression of genes relating to PI3K, MAPK and/or Wnt pathway signaling (kirsten rat sarcoma 2 viral oncogene homolog [KRAS] and PTEN protein). Biopsies were obtained at baseline and Cycle 1 Day 23. Biomarker evaluation was performed on these biopsies.
Time Frame Baseline and Cycle 1 Day 23.

Outcome Measure Data

Analysis Population Description
All enrolled participants who started treatment and had baseline tumor tissues successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Measure Participants 5 1 1 6 7 3 5 4 24 4 2 3 6 7 3 2 1
KRAS mutation
4
80%
1
100%
1
100%
0
0%
3
42.9%
0
0%
2
33.3%
1
25%
10
32.3%
2
28.6%
1
33.3%
2
50%
4
57.1%
6
85.7%
2
66.7%
1
25%
1
50%
PTEN tumor manual score
4
80%
1
100%
1
100%
5
71.4%
6
85.7%
3
100%
5
83.3%
4
100%
24
77.4%
4
57.1%
2
66.7%
3
75%
6
85.7%
7
100%
2
66.7%
2
50%
1
50%
PTEN stroma manual score
4
80%
1
100%
1
100%
5
71.4%
6
85.7%
3
100%
4
66.7%
4
100%
24
77.4%
4
57.1%
2
66.7%
3
75%
6
85.7%
7
100%
2
66.7%
2
50%
1
50%
45. Secondary Outcome
Title Duration of Response (Stage 2)
Description Duration of response was to be calculated for participants with an objective response. Duration of PR or CR was the time from start date (date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR: disappearance of a target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.
Time Frame Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until until progression of disease was documented.

Outcome Measure Data

Analysis Population Description
There was only 1 participant in Arm C1 and 1 in Arm C2 with a response, therefore summary statistics were not calculated for this endpoint.
Arm/Group Title PF-05212384+Irinotecan: Arm C2 (Stage 2)
Arm/Group Description Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Measure Participants 0

Adverse Events

Time Frame Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration).
Adverse Event Reporting Description
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+ PD-0325901: Arm D1B (Stage 1)) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
All Cause Mortality
PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+ PD-0325901: Arm D1B (Stage 1)) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+ PD-0325901: Arm D1B (Stage 1)) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/5 (40%) 1/1 (100%) 1/1 (100%) 2/7 (28.6%) 5/7 (71.4%) 0/3 (0%) 0/6 (0%) 2/4 (50%) 5/31 (16.1%) 3/7 (42.9%) 1/3 (33.3%) 2/4 (50%) 4/7 (57.1%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Blood and lymphatic system disorders
Febrile neutropenia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cardiac disorders
Cardiac tamponade 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gastrointestinal disorders
Diarrhoea 1/5 (20%) 1/1 (100%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gastrointestinal haemorrhage 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Intestinal obstruction 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Small intestinal obstruction 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
General disorders
Disease progression 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Mucosal inflammation 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Fatigue 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Pyrexia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Asthenia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hepatobiliary disorders
Cholestasis 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hepatic function abnormal 0/5 (0%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cholangitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cholecystitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Infections and infestations
Escherichia bacteraemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gastroenteritis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Sepsis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Skin infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Anal abscess 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Lung infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Device related infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Respiratory tract infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Investigations
Transaminases increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Metabolism and nutrition disorders
Hypokalaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dehydration 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hypercalcaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/5 (0%) 1/1 (100%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Back pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Nervous system disorders
Ischaemic stroke 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Other (Not Including Serious) Adverse Events
PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+ PD-0325901: Arm D1B (Stage 1)) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/5 (100%) 1/1 (100%) 1/1 (100%) 7/7 (100%) 7/7 (100%) 3/3 (100%) 6/6 (100%) 4/4 (100%) 31/31 (100%) 7/7 (100%) 3/3 (100%) 4/4 (100%) 7/7 (100%) 7/7 (100%) 3/3 (100%) 4/4 (100%) 2/2 (100%)
Blood and lymphatic system disorders
Anaemia 0/5 (0%) 1/1 (100%) 1/1 (100%) 0/7 (0%) 1/7 (14.3%) 1/3 (33.3%) 1/6 (16.7%) 0/4 (0%) 7/31 (22.6%) 1/7 (14.3%) 1/3 (33.3%) 2/4 (50%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Neutropenia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 4/31 (12.9%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Leukopenia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Normochromic normocytic anaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Thrombocytopenia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cardiac disorders
Sinus bradycardia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Tachycardia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Arrhythmia 0/5 (0%) 1/1 (100%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Bradycardia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Ear and labyrinth disorders
Ear disorder 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Ear pain 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Ear discomfort 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Eustachian tube dysfunction 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Middle ear effusion 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Motion sickness 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Endocrine disorders
Hypothyroidism 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Eye disorders
Lacrimation increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Photophobia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dry eye 2/5 (40%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Iridocyclitis 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Retinal detachment 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Vision blurred 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Visual acuity reduced 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Chorioretinopathy 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Eye pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Eyelid oedema 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Periorbital oedema 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 2/7 (28.6%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Retinopathy 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Visual impairment 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gastrointestinal disorders
Diarrhoea 5/5 (100%) 1/1 (100%) 0/1 (0%) 3/7 (42.9%) 3/7 (42.9%) 1/3 (33.3%) 2/6 (33.3%) 3/4 (75%) 17/31 (54.8%) 1/7 (14.3%) 1/3 (33.3%) 2/4 (50%) 3/7 (42.9%) 5/7 (71.4%) 0/3 (0%) 1/4 (25%) 1/2 (50%)
Dyspepsia 0/5 (0%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 1/3 (33.3%) 1/4 (25%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Nausea 3/5 (60%) 1/1 (100%) 0/1 (0%) 5/7 (71.4%) 5/7 (71.4%) 3/3 (100%) 3/6 (50%) 2/4 (50%) 19/31 (61.3%) 1/7 (14.3%) 2/3 (66.7%) 1/4 (25%) 3/7 (42.9%) 5/7 (71.4%) 0/3 (0%) 1/4 (25%) 1/2 (50%)
Stomatitis 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 1/6 (16.7%) 1/4 (25%) 6/31 (19.4%) 2/7 (28.6%) 1/3 (33.3%) 1/4 (25%) 0/7 (0%) 4/7 (57.1%) 2/3 (66.7%) 1/4 (25%) 0/2 (0%)
Vomiting 1/5 (20%) 1/1 (100%) 0/1 (0%) 6/7 (85.7%) 4/7 (57.1%) 1/3 (33.3%) 3/6 (50%) 2/4 (50%) 14/31 (45.2%) 2/7 (28.6%) 1/3 (33.3%) 2/4 (50%) 3/7 (42.9%) 5/7 (71.4%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Abdominal pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 3/7 (42.9%) 0/7 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/4 (0%) 12/31 (38.7%) 2/7 (28.6%) 1/3 (33.3%) 1/4 (25%) 1/7 (14.3%) 2/7 (28.6%) 1/3 (33.3%) 1/4 (25%) 0/2 (0%)
Abdominal pain upper 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/3 (33.3%) 2/6 (33.3%) 1/4 (25%) 2/31 (6.5%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Constipation 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 7/31 (22.6%) 2/7 (28.6%) 1/3 (33.3%) 3/4 (75%) 3/7 (42.9%) 3/7 (42.9%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dry mouth 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 1/7 (14.3%) 1/3 (33.3%) 1/4 (25%) 2/7 (28.6%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 1/2 (50%)
Abdominal discomfort 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cheilitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dysphagia 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Frequent bowel movements 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Haemorrhoids 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Oral pain 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 3/31 (9.7%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Abdominal distension 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Anal inflammation 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Flatulence 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gastric disorder 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gastrooesophageal reflux disease 2/5 (40%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gingival pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Intestinal obstruction 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Odynophagia 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Proctalgia 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Rectal haemorrhage 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Toothache 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Abdominal pain lower 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
General disorders
Asthenia 0/5 (0%) 0/1 (0%) 1/1 (100%) 2/7 (28.6%) 2/7 (28.6%) 0/3 (0%) 1/6 (16.7%) 1/4 (25%) 10/31 (32.3%) 2/7 (28.6%) 2/3 (66.7%) 2/4 (50%) 0/7 (0%) 1/7 (14.3%) 1/3 (33.3%) 2/4 (50%) 0/2 (0%)
Fatigue 3/5 (60%) 1/1 (100%) 0/1 (0%) 3/7 (42.9%) 3/7 (42.9%) 2/3 (66.7%) 2/6 (33.3%) 2/4 (50%) 9/31 (29%) 3/7 (42.9%) 1/3 (33.3%) 0/4 (0%) 4/7 (57.1%) 5/7 (71.4%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Pain 1/5 (20%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Pyrexia 1/5 (20%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 1/6 (16.7%) 2/4 (50%) 6/31 (19.4%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 2/7 (28.6%) 3/7 (42.9%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Oedema peripheral 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 5/31 (16.1%) 0/7 (0%) 1/3 (33.3%) 3/4 (75%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Catheter site rash 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Mucosal inflammation 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 2/3 (66.7%) 1/6 (16.7%) 1/4 (25%) 5/31 (16.1%) 1/7 (14.3%) 1/3 (33.3%) 1/4 (25%) 4/7 (57.1%) 3/7 (42.9%) 1/3 (33.3%) 1/4 (25%) 2/2 (100%)
Catheter site inflammation 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Catheter site ulcer 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Chest pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Chills 1/5 (20%) 1/1 (100%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 2/7 (28.6%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Disease progression 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Early satiety 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gait disturbance 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Injection site mass 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Malaise 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Non-cardiac chest pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Thirst 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hepatobiliary disorders
Cholelithiasis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hepatomegaly 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Hyperbilirubinaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Jaundice 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Immune system disorders
Drug hypersensitivity 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Seasonal allergy 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Infections and infestations
Urinary tract infection 2/5 (40%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 5/31 (16.1%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 1/7 (14.3%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Nasopharyngitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 1/4 (25%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Device related infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gingivitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Sinusitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Anal infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Bronchitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Candida infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Catheter site infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Clostridium difficile colitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Herpes simplex 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Infection 0/5 (0%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Joint abscess 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Laryngitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Lung infection 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Oral candidiasis 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Respiratory tract infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Rhinitis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Skin infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Stoma site infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Upper respiratory tract infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Vaginal infection 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Injury, poisoning and procedural complications
Contusion 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Corneal abrasion 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Fall 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Laceration 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Investigations
Alanine aminotransferase increased 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 2/7 (28.6%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Aspartate aminotransferase increased 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 3/31 (9.7%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 2/7 (28.6%) 1/7 (14.3%) 2/3 (66.7%) 0/4 (0%) 0/2 (0%)
Weight decreased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 3/31 (9.7%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Blood bilirubin increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Blood creatinine increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Electrocardiogram QT prolonged 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Neutrophil count decreased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 5/31 (16.1%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Blood alkaline phosphatase increased 0/5 (0%) 0/1 (0%) 1/1 (100%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Blood calcium increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Blood iron decreased 0/5 (0%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Ejection fraction decreased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Gamma-glutamyltransferase increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Troponin T increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite 0/5 (0%) 1/1 (100%) 1/1 (100%) 4/7 (57.1%) 4/7 (57.1%) 2/3 (66.7%) 1/6 (16.7%) 3/4 (75%) 12/31 (38.7%) 2/7 (28.6%) 1/3 (33.3%) 1/4 (25%) 1/7 (14.3%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Dehydration 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 4/31 (12.9%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 1/2 (50%)
Hypokalaemia 1/5 (20%) 1/1 (100%) 1/1 (100%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 3/31 (9.7%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 1/7 (14.3%) 3/7 (42.9%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hyperglycaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/3 (33.3%) 1/6 (16.7%) 1/4 (25%) 5/31 (16.1%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Hypomagnesaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hypovolaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cachexia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Fluid retention 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hyperuricaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hypoalbuminaemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hyponatraemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 2/7 (28.6%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/2 (50%)
Hypophosphataemia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Musculoskeletal and connective tissue disorders
Back pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 6/31 (19.4%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Musculoskeletal chest pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 3/31 (9.7%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Pain in extremity 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Arthralgia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Bone pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Costochondritis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Fistula discharge 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Flank pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Muscle fatigue 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Muscle spasms 1/5 (20%) 1/1 (100%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Muscle twitching 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Muscular weakness 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Musculoskeletal pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Neck pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cancer pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Nervous system disorders
Headache 1/5 (20%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 5/31 (16.1%) 2/7 (28.6%) 0/3 (0%) 1/4 (25%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Tremor 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dizziness 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 2/7 (28.6%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dysgeusia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 4/31 (12.9%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 1/2 (50%)
Hypoaesthesia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hypogeusia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Ischaemic stroke 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Neurotoxicity 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Presyncope 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Psychiatric disorders
Depressed mood 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Abnormal behaviour 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Abnormal dreams 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Confusional state 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Depression 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hallucination 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Insomnia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 3/7 (42.9%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Renal and urinary disorders
Proteinuria 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 2/6 (33.3%) 0/4 (0%) 1/31 (3.2%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Choluria 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dysuria 0/5 (0%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Pollakiuria 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Renal pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Urinary retention 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Reproductive system and breast disorders
Vulvovaginal pruritus 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 1/13 (7.7%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Ejaculation failure 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 3/5 (60%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 3/3 (100%) 1/6 (16.7%) 0/4 (0%) 1/31 (3.2%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 3/7 (42.9%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Epistaxis 1/5 (20%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hiccups 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Bronchiectasis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 1/4 (25%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Cough 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 2/6 (33.3%) 1/4 (25%) 3/31 (9.7%) 1/7 (14.3%) 2/3 (66.7%) 1/4 (25%) 1/7 (14.3%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Dysphonia 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Oropharyngeal pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 1/4 (25%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Pleural effusion 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 2/31 (6.5%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Pleuritic pain 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Productive cough 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Sputum increased 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dyspnoea exertional 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 2/7 (28.6%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Haemoptysis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Nasal congestion 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Rhinorrhoea 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Skin and subcutaneous tissue disorders
Pruritus 1/5 (20%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 3/31 (9.7%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 1/2 (50%)
Rash 2/5 (40%) 0/1 (0%) 1/1 (100%) 2/7 (28.6%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 1/4 (25%) 7/31 (22.6%) 2/7 (28.6%) 0/3 (0%) 1/4 (25%) 3/7 (42.9%) 1/7 (14.3%) 1/3 (33.3%) 3/4 (75%) 2/2 (100%)
Alopecia 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 2/7 (28.6%) 1/3 (33.3%) 2/6 (33.3%) 0/4 (0%) 7/31 (22.6%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dermatitis acneiform 2/5 (40%) 1/1 (100%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/6 (16.7%) 0/4 (0%) 0/31 (0%) 3/7 (42.9%) 2/3 (66.7%) 1/4 (25%) 3/7 (42.9%) 4/7 (57.1%) 2/3 (66.7%) 0/4 (0%) 0/2 (0%)
Nail bed disorder 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Rash maculo-papular 2/5 (40%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 2/6 (33.3%) 0/4 (0%) 1/31 (3.2%) 3/7 (42.9%) 1/3 (33.3%) 1/4 (25%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Dermatitis contact 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Dry skin 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 1/7 (14.3%) 2/7 (28.6%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Eczema 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Erythema 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 2/7 (28.6%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 1/2 (50%)
Hair colour changes 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hyperhidrosis 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Night sweats 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/4 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Palmar-plantar erythrodysaesthesia syndrome 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Pruritus generalised 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Rash erythematous 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Rash macular 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/2 (0%)
Rash papular 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 2/4 (50%) 0/7 (0%) 0/7 (0%) 2/3 (66.7%) 1/4 (25%) 0/2 (0%)
Rash pruritic 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Scab 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Skin fissures 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/2 (0%)
Skin hyperpigmentation 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Skin lesion 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Skin ulcer 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Vascular disorders
Flushing 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 2/3 (66.7%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hypertension 0/5 (0%) 0/1 (0%) 1/1 (100%) 0/7 (0%) 0/7 (0%) 1/3 (33.3%) 0/6 (0%) 0/4 (0%) 1/31 (3.2%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 2/7 (28.6%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Embolism 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Hot flush 0/5 (0%) 0/1 (0%) 0/1 (0%) 1/7 (14.3%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Lymphoedema 1/5 (20%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Pallor 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 1/7 (14.3%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 1/3 (33.3%) 0/4 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)
Venous thrombosis limb 0/5 (0%) 0/1 (0%) 0/1 (0%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/6 (0%) 0/4 (0%) 0/31 (0%) 0/7 (0%) 0/3 (0%) 1/4 (25%) 0/7 (0%) 0/7 (0%) 0/3 (0%) 0/4 (0%) 0/2 (0%)

Limitations/Caveats

This study was terminated prematurely for strategic reasons based on an internal portfolio prioritization.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01347866
Other Study ID Numbers:
  • B1271002
  • 2011-001671-39
First Posted:
May 4, 2011
Last Update Posted:
Oct 29, 2018
Last Verified:
Feb 1, 2018