Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02109445
• Collaborator: Academic GI Cancer Consortium (AGICC) (Other)
• Enrollment: 3
• Locations: 5
• Arms: 3
• Actual Duration (Months): 2.1
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study consists of a Phase 1b portion aimed to determine the maximum tolerated dose and the safety profile of PF-03084014 in combination with gemcitabine and nab-paclitaxel followed by a Phase 2 portion to evaluate the efficacy of the triple combination in terms of overall survival in patients with metastatic pancreatic ductal adenocarcinoma not previously treated with anticancer therapies.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cancer Pancreas	Drug: PF-03084014; Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: PF-03084014; Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Nab-paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PHASE 1/2 STUDY OF PF-03084014 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
• Actual Study Start Date: Sep 3, 2014
• Actual Primary Completion Date: Nov 6, 2014
• Actual Study Completion Date: Nov 6, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 PF-03084014 in combination with gemcitabine and nab-paclitaxel	Drug: PF-03084014; Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Doses: 100 -150 mg BID; Drug: Gemcitabine; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.; Drug: Nab-paclitaxel; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.; Other Names: Abraxane
Experimental: Phase 2 Arm A PF-03084014 in combination with gemcitabine and nab-paclitaxel	Drug: PF-03084014; Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Phase 2 dose will be the recommended phase 2 dose defined in phase 1.; Drug: Gemcitabine; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.; Drug: Nab-paclitaxel; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.; Other Names: Abraxane
Active Comparator: Phase 2 Arm B Gemcitabine plus nab-Paclitaxel	Drug: Gemcitabine; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.; Drug: Nab-paclitaxel; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.; Other Names: Abraxane

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1 [Cycle 1 (28 days)]

   DLT was defined as any of the following events occurring during the first cycle of treatment and considered at least possibly-related to study medication: any Grade 3 or 4 clinically-relevant non-hematologic and/or hematologic toxicity, delay of more than 2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.

2. Overall Survival (OS) in Phase 2 [From start of study treatment, collected every 3 months until death (up to 5 years)]

   Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

Secondary Outcome Measures

1. Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1 [Baseline up to 28-35 days post last administration of study drug]

   Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.

2. Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2 [Baseline up to 28-35 days post last administration of study drug]

   Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.

3. Number of Participants With Laboratory Abnormalities in Phase 1 [Screening; Cycle 1 Days 1, 8, 15, 22; up to 28-35 days post last administration of study drug]

   Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).

4. Number of Participants With Laboratory Abnormalities in Phase 2 [Screening; Days 1, 8, 15 of each cycle; up to 28-35 days post last administration of study drug]

   Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).

5. Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2 [Baseline up to 28-35 days after treatment discontinuation]

   Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, heart rate, weight and body surface area.

6. Number of Participants With Worsening QTc Results in Phase 1 [Screening, Cycle 1 Days 3 and 22, Cycles 2 and 3 Day 1, end of treatment]

   Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.

7. Number of Participants With Worsening QTc Results in Phase 2 [Screening, Cycle 1 Days 1 and 22, Cycles 2 and 3 Day 1, end of treatment]

   Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.

8. Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 1 [PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.]

   AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau, tau=12 hours), and AUC from time 0 to last measured concentration (AUClast).

9. Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 2 [Cycle 1 Day 1 till end of last cycle]

   AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau), and AUC from time 0 to last measured concentration (AUClast).

10. Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 1 [PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.]

11. Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 2 [Cycle 1 Day 1 till end of last cycle]

12. Systemic Clearance (CL) of Nab-paclitaxel in Phase 1 [Cycle 1 Days 1-3, and 15-17]

13. Systemic Clearance (CL) of Gemcitabine in Phase 1 [Cycle 1 Days 1 and 15]

14. Systemic Clearance (CL) of PF-03084014, Nab-P and GEM in Phase 2 [Cycle 1 Day 1 till end of last cycle]

15. Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 1 [PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.]

16. Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 2 [Cycle 1 Day 1 till end of last cycle]

17. Volume of Distribution at Steady State (Vss) for Nab-P and GEM in Phase 1 [Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)]

18. Volume of Distribution at Steady State (Vss) for PF-03084014, Nab-P and GEM in Phase 2 [Cycle 1 Day 1 till end of last cycle]

19. Plasma Decay Half-life (t1/2) for Nab-P and GEM in Phase 1 [Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)]

20. Plasma Decay Half-life (t1/2) for PF-03084014, Nab-P and GEM in Phase 2 [Cycle 1 Day 1 till end of last cycle]

21. Number of Participants With Objective Response (OR) in Phase 1 [Screening till 28-35 days post last administration of study drug]

    Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

22. Number of Participants With Objective Response (OR) in Phase 2 [Screening till 28-35 days post last administration of study drug]

    Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

23. Duration of Response (DR) for Phases 1 and 2 [Baseline, every 8 weeks until disease progression or unacceptable toxicity (up to 5 years)]

    Duration of response (DR) defined as the difference in days between the first date criteria for progression occurred or the participant died due to any cause and the first date that criteria for a PR or CR were met. DR calculated as (months) = (progression/death date - first date of OR + 1) divided by 30.4. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

24. 1-year and 2-year OS in Phase 2 [From start of study treatment, collected every 3 months until death (up to 5 years)]

    Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

25. Progression-free Survival (PFS) in Phase 2 [From start of study treatment, collected every 3 months until death (up to 5 years)]

    PFS was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first. PFS (in months) was calculated as (first event date - date of randomization +1) divided by 30.4.

26. Brief Pain Inventory-Short Form (BPI-sf) Score - Phase 2 [Day 1 of Cycle 1 and subsequent cycles; end of treatment]

    BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.

27. Change From Baseline in European Quality of Life Questionnaire (EQ-5D) - Phase 2 [Baseline till end of treatment]

    EQ-5D: 6-item participant rated questionnaire to assess health-related quality of life in terms of a single utility score. There were 2 components: a Health State Profile and a Visual Analog Scale. Published weights are available that allow for the creation of a single summary score. Overall scores range from 0-1, with low scores representing a higher level of dysfunction.

28. European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) - Phase 2 [Baseline till end of treatment]

    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically diagnosis of metastatic ductal adenocarcinoma of the pancreas.

• No prior radiotherapy, surgery chemotherapy or investigational therapy for metastatic disease. Prior adjuvant therapy with 5-FU or gemcitabine (± gemcitabine post radiation) administered as radiosensitizer allowed, provided at least 6 months have elapsed between the last dose and study registration

• Tumor tissue available (Archival 6 months old or de novo biopsy)

• Measurable disease as per RECIST 1.1

• Performance Status (ECOG) 0 or 1

Exclusion Criteria:

• Symptomatic brain metastases requiring steroids

• Prior therapy with gamma secretase inhibitors or other Notch pathway inhibitor

• Major surgery within 4 weeks of registration in the current study

• Known hypersensitivity to gemcitabine or nab-paclitaxel or any of the excipients

• Current or anticipated need for food or drugs that are strong/moderate CYP3A4 inhibitors or inducers

• Diagnosis of any second malignancy within 3 years prior to registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anschutz Inpatient Pavilion	Aurora	Colorado	United States	80045
2	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
3	University of Colorado Denver, CTO (CTRC)	Aurora	Colorado	United States	80045
4	University of Rochester Investigational Drug Pharmacy	Rochester	New York	United States	14642
5	University of Rochester	Rochester	New York	United States	14642

Sponsors and Collaborators

• Pfizer
• Academic GI Cancer Consortium (AGICC)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02109445
• Other Study ID Numbers: A8641019; 2013-005574-21
• First Posted: Apr 9, 2014
• Last Update Posted: Jan 10, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	The study planned to include 2 phases: Phase 1 (dose-finding phase) followed by Phase 2 (randomized phase). Due to early termination of the study, only 3 participants were enrolled in Phase 1 and Phase 2 was not conducted.

Arm/Group Title	PF-03084014+Nab-Paclitaxel+Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	PF-03084014+Nab-Paclitaxel+Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Overall Participants	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.3 (4.7)
Sex: Female, Male (Count of Participants)
Female	2 66.7%
Male	1 33.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
Description	DLT was defined as any of the following events occurring during the first cycle of treatment and considered at least possibly-related to study medication: any Grade 3 or 4 clinically-relevant non-hematologic and/or hematologic toxicity, delay of more than 2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.
Time Frame	Cycle 1 (28 days)

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study treatment and who either experienced DLT during the first cycle, or completed the 1-cycle observation period, were considered evaluable for DLT. Only 2 of the 3 participants were evaluable for DLTs.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	2
Number [participants]	2 66.7%

2. Primary Outcome

Title	Overall Survival (OS) in Phase 2
Description	Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame	From start of study treatment, collected every 3 months until death (up to 5 years)

Outcome Measure Data

Analysis Population Description

All randomized participants in Phase 2 were to be analyzed for OS. However, since Phase 2 was not carried out due to early termination, no subjects were analyzed for OS.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

3. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1
Description	Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.
Time Frame	Baseline up to 28-35 days post last administration of study drug

Outcome Measure Data

Analysis Population Description

All enrolled participants in Phase 1 who received at least 1 dose of study medication.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
All-causality TEAEs	3 100%
Treatment-related TEAEs	3 100%
Grade 3 or 4 TEAEs	3 100%

4. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2
Description	Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.
Time Frame	Baseline up to 28-35 days post last administration of study drug

Outcome Measure Data

Analysis Population Description

No participants were analyzed since Phase 2 was not performed.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

5. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities in Phase 1
Description	Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).
Time Frame	Screening; Cycle 1 Days 1, 8, 15, 22; up to 28-35 days post last administration of study drug

Outcome Measure Data

Analysis Population Description

All participants who received any study treatment.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Number [participants]	3 100%

6. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities in Phase 2
Description	Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).
Time Frame	Screening; Days 1, 8, 15 of each cycle; up to 28-35 days post last administration of study drug

Outcome Measure Data

Analysis Population Description

Due to early termination, Phase 2 was not performed and thus no participants were included in this analysis.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

7. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2
Description	Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, heart rate, weight and body surface area.
Time Frame	Baseline up to 28-35 days after treatment discontinuation

Outcome Measure Data

Analysis Population Description

All enrolled participants in Phase 1, or all randomized participants in Phase 2, who received at least 1 dose of study medication. Due to early termination of the study, vital sign evaluations were not performed.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

8. Secondary Outcome

Title	Number of Participants With Worsening QTc Results in Phase 1
Description	Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.
Time Frame	Screening, Cycle 1 Days 3 and 22, Cycles 2 and 3 Day 1, end of treatment

Outcome Measure Data

Analysis Population Description

All enrolled participants in Phase 1 who had at least 1 ECG assessment after receiving PF-03084014.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Number [participants]	NA NaN

9. Secondary Outcome

Title	Number of Participants With Worsening QTc Results in Phase 2
Description	Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.
Time Frame	Screening, Cycle 1 Days 1 and 22, Cycles 2 and 3 Day 1, end of treatment

Outcome Measure Data

Analysis Population Description

Due to early termination, Phase 2 was not performed and thus no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

10. Secondary Outcome

Title	Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 1
Description	AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau, tau=12 hours), and AUC from time 0 to last measured concentration (AUClast).
Time Frame	PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the pharmacokinetic (PK) parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
AUClast for PF-03084014 on Day 3 (n=3)	1122 (913)
AUClast for PF-03084014 on Day 15 (n=1)	1770 (NA)
AUCinf for nab-paclitaxel on Day 1 (n=3)	5774 (11)
AUClast for nab-paclitaxel on Day 1 (n=3)	5185 (9)
AUCinf for nab-paclitaxel on Day 15 (n=1)	5050 (NA)
AUClast for nab-paclitaxel on Day 15 (n=1)	4600 (NA)
AUCinf for gemcitabine on Day 1 (n=3)	5316 (172)
AUClast for gemcitabine on Day 1 (n=3)	5262 (176)
AUCinf for gemcitabine on Day 15 (n=1)	2510 (NA)
AUClast for gemcitabine on Day 15 (n=1)	2500 (NA)

11. Secondary Outcome

Title	Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 2
Description	AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau), and AUC from time 0 to last measured concentration (AUClast).
Time Frame	Cycle 1 Day 1 till end of last cycle

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed, no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

12. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 1
Time Frame	PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Cmax for PF-03084014 on Day 3 (n=3)	527.3 (710)
Cmax for PF-03084014 on Day 15 (n=1)	943.0 (NA)
Cmax for nab-paclitaxel on Day 1 (n=3)	6023 (6)
Cmax for nab-paclitaxel on Day 15 (n=1)	5140 (NA)
Cmax for gemcitabine on Day 1 (n=3)	10760 (212)
Cmax for gemcitabine on Day 15 (n=1)	3620 (NA)

13. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame	Cycle 1 Day 1 till end of last cycle

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed, no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

14. Secondary Outcome

Title	Systemic Clearance (CL) of Nab-paclitaxel in Phase 1
Time Frame	Cycle 1 Days 1-3, and 15-17

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Day 1 (n=3)	37.88 (25)
Day 15 (n=1)	38.60 (NA)

15. Secondary Outcome

Title	Systemic Clearance (CL) of Gemcitabine in Phase 1
Time Frame	Cycle 1 Days 1 and 15

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Day 1 (n=3)	5.434 (165)
Day 15 (n=1)	8.160 (NA)

16. Secondary Outcome

Title	Systemic Clearance (CL) of PF-03084014, Nab-P and GEM in Phase 2
Time Frame	Cycle 1 Day 1 till end of last cycle

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed, no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

17. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 1
Time Frame	PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Tmax of PF-03084014 on Day 3 (n=3)	1.23
Tmax of PF-03084014 on Day 15 (n=1)	0.900
Tmax of nab-paclitaxel on Day 1 (n=3)	0.550
Tmax of nab-paclitaxel on Day 15 (n=1)	0.217
Tmax of gemcitabine on Day 1 (n=3)	0.517
Tmax of gemcitabine on Day 15 (n=1)	0.350

18. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame	Cycle 1 Day 1 till end of last cycle

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed, no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

19. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) for Nab-P and GEM in Phase 1
Time Frame	Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
Vss of nab-paclitaxel on Day 1 (n=3)	64.46 (6)
Vss of nab-paclitaxel on Day 15 (n=1)	60.80 (NA)
Vss of gemcitabine on Day 1 (n=3)	61.76 (186)
Vss of gemcitabine on Day 15 (n=1)	201.0 (NA)

20. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame	Cycle 1 Day 1 till end of last cycle

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed, no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

21. Secondary Outcome

Title	Plasma Decay Half-life (t1/2) for Nab-P and GEM in Phase 1
Time Frame	Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)

Outcome Measure Data

Analysis Population Description

All treated participants who had at least 1 of the PK parameters of interest of any of the study drugs. n=number of evaluable participants for that parameter at the specified time point.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	3
t1/2 of nab-paclitaxel on Day 1 (n=3)	2.500 (0.26851)
t1/2 of nab-paclitaxel on Day 15 (n=1)	2.030 (NA)
t1/2 of gemcitabine on Day 1 (n=3)	0.2813 (0.14838)
t1/2 of gemcitabine on Day 15 (n=1)	0.2230 (NA)

22. Secondary Outcome

Title	Plasma Decay Half-life (t1/2) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame	Cycle 1 Day 1 till end of last cycle

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed, no participants were analyzed for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

23. Secondary Outcome

Title	Number of Participants With Objective Response (OR) in Phase 1
Description	Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame	Screening till 28-35 days post last administration of study drug

Outcome Measure Data

Analysis Population Description

All enrolled participants in Phase 1 who were eligible for enrollment, received study treatment, had measurable disease and adequate baseline assessments, and had at least 1 on-study tumor assessment, were considered evaluable for response. Only 1 participant was evaluable for OR in Phase 1.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	1
Number [participants]	0 0%

24. Secondary Outcome

Title	Number of Participants With Objective Response (OR) in Phase 2
Description	Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame	Screening till 28-35 days post last administration of study drug

Outcome Measure Data

Analysis Population Description

No participants were analyzed for this outcome measure as Phase 2 was not done.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

25. Secondary Outcome

Title	Duration of Response (DR) for Phases 1 and 2
Description	Duration of response (DR) defined as the difference in days between the first date criteria for progression occurred or the participant died due to any cause and the first date that criteria for a PR or CR were met. DR calculated as (months) = (progression/death date - first date of OR + 1) divided by 30.4. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.
Time Frame	Baseline, every 8 weeks until disease progression or unacceptable toxicity (up to 5 years)

Outcome Measure Data

Analysis Population Description

No participants were analyzed for this outcome measure as there were no participants with OR in Phase 1 and Phase 2 was not done.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

26. Secondary Outcome

Title	1-year and 2-year OS in Phase 2
Description	Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame	From start of study treatment, collected every 3 months until death (up to 5 years)

Outcome Measure Data

Analysis Population Description

All randomized participants in Phase 2 were to be analyzed for OS. However, since Phase 2 was not carried out due to early termination, no subjects were analyzed for OS.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

27. Secondary Outcome

Title	Progression-free Survival (PFS) in Phase 2
Description	PFS was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first. PFS (in months) was calculated as (first event date - date of randomization +1) divided by 30.4.
Time Frame	From start of study treatment, collected every 3 months until death (up to 5 years)

Outcome Measure Data

Analysis Population Description

All randomized participants in Phase 2 were to be analyzed for PFS. However, since Phase 2 was not carried out due to early termination, no subjects were analyzed for PFS.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

28. Secondary Outcome

Title	Brief Pain Inventory-Short Form (BPI-sf) Score - Phase 2
Description	BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Time Frame	Day 1 of Cycle 1 and subsequent cycles; end of treatment

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed due to early termination, there were no participants to analyse for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

29. Secondary Outcome

Title	Change From Baseline in European Quality of Life Questionnaire (EQ-5D) - Phase 2
Description	EQ-5D: 6-item participant rated questionnaire to assess health-related quality of life in terms of a single utility score. There were 2 components: a Health State Profile and a Visual Analog Scale. Published weights are available that allow for the creation of a single summary score. Overall scores range from 0-1, with low scores representing a higher level of dysfunction.
Time Frame	Baseline till end of treatment

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed due to early termination, there were no participants to analyse for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

30. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) - Phase 2
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Time Frame	Baseline till end of treatment

Outcome Measure Data

Analysis Population Description

As Phase 2 was not performed due to early termination, there were no participants to analyse for this outcome measure.

Arm/Group Title	PF-03084014 + Nab-Paclitaxel + Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
Measure Participants	0

Adverse Events

Time Frame	Baseline through and including 28 calendar days after the last administration of the investigational product.
Arm/Group Title	PF-03084014+Nab-Paclitaxel+Gemcitabine
Arm/Group Description	PF-03084014 was administered twice daily (BID) orally via tablets at a starting dose of 100 milligrams (mg). Nab-paclitaxel (nab-P) and gemcitabine (GEM) were administered intravenously at a starting dose of 125 mg/square meter (m^2) and 1000 mg/m^2, respectively. Decisions to escalate, de-escalate or stay at the same dose were made based on the number of dose-limiting toxicities (DLTs) observed. In any case, PF-03084014 dose was not to exceed 150 mg BID and nab-P and GEM were not to exceed 125 mg/m^2 and 1000 mg/m^2, respectively.
All Cause Mortality
	PF-03084014+Nab-Paclitaxel+Gemcitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PF-03084014+Nab-Paclitaxel+Gemcitabine
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Gastrointestinal disorders
Vomiting	1/3 (33.3%)
Investigations
Alanine aminotransferase increased	1/3 (33.3%)
Aspartate aminotransferase increased	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	PF-03084014+Nab-Paclitaxel+Gemcitabine
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Gastrointestinal disorders
Ascites	1/3 (33.3%)
Nausea	2/3 (66.7%)
Vomiting	2/3 (66.7%)
General disorders
Chills	1/3 (33.3%)
Fatigue	3/3 (100%)
Mucosal inflammation	1/3 (33.3%)
Infections and infestations
Candida infection	1/3 (33.3%)
Injury, poisoning and procedural complications
Fall	1/3 (33.3%)
Investigations
Alanine aminotransferase increased	2/3 (66.7%)
Aspartate aminotransferase increased	2/3 (66.7%)
Blood bilirubin increased	1/3 (33.3%)
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)
Failure to thrive	1/3 (33.3%)
Hypokalaemia	1/3 (33.3%)
Hypophosphataemia	1/3 (33.3%)
Nervous system disorders
Dizziness	1/3 (33.3%)
Psychiatric disorders
Anxiety	1/3 (33.3%)
Depression	1/3 (33.3%)
Hallucination	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)
Pleural effusion	1/3 (33.3%)
Skin and subcutaneous tissue disorders
Rash	1/3 (33.3%)

Limitations/Caveats

Due to early termination of the study, only 3 participants were enrolled. Phase 2 was not carried out. As such, there is limited data for Phase 1 and no data for Phase 2.

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.