A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02299635
• Collaborator: (none)
• Enrollment: 19
• Locations: 37
• Arm: 1
• Actual Duration (Months): 11.3
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is designed to evaluate the preliminary anti-tumor activity and tolerability of PF-03084014 when administered as a single agent in the treatment of patients with advanced triple receptor-negative breast cancer (mTNBC) harboring genomic alterations in Notch receptors (NA+), and in a smaller subset of mTNBC patients whose tumor tests negative for genomic alterations in Notch receptors (NA-)

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Neoplasms	Drug: PF-03084014; Drug: PF-03084014; Drug: PF-03084014	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PHASE 2 STUDY OF SINGLE-AGENT PF-03084014 IN PATIENTS WITH ADVANCED TRIPLE-NEGATIVE BREAST CANCER WITH OR WITHOUT GENOMIC ALTERATIONS IN NOTCH RECEPTORS
• Actual Study Start Date: Feb 3, 2015
• Actual Primary Completion Date: Jan 14, 2016
• Actual Study Completion Date: Jan 14, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-03084014 PF-03084014 will be administered orally, continuously, twice daily at 150 mg, but the dose can be reduced to 100 mg or 80 mg.	Drug: PF-03084014; Tablet, 10 mg, twice a day.; Drug: PF-03084014; Tablet, 50 mg, twice a day; Drug: PF-03084014; Tablet, 100 mg, twice a day

Outcome Measures

Primary Outcome Measures

1. Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+) [Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.]

   OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis less than [<]10 millimeter [mm]). PR: Greater than or equal to (>=)30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.

Secondary Outcome Measures

1. OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-) [Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.]

   OR status based on assessment of confirmed CR or confirmed PR according to RECIST 1.1. CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis <10 mm). PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.

2. Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC [2 years]

   The period from study entry until disease progression, death, whichever occurred first as per RECIST version 1.1.

3. Duration of Response (DR) in Participants With NA+ or NA mTNBC [2 years]

   Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated for the subgroup of patients with a confirmed objective tumor response. Objective Progression (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.

4. One-Year Survival Probability in Participants With NA+ or NA mTNBC [1 year]

   Overall survival (OS) status (alive or not) at 1 year after study entry. The the survival probability at 1 year was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.

5. Overall Survival (OS) in Participants With NA+ or NA mTNBC [2 years]

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

6. Type of Notch Genomic Alterations in Participants With NA+ mTNBC [2 years]

   Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC

7. Pre-dose Serum Concentration (Ctrough) for PF-03084014 [Day 1 of Cycle 1, 2, 3, and 5]

8. Pharmacodynamic (PD) Effects of PF-03084014 in Tumor Specimens and Peripheral Blood [Day 1 of Cycle 1, 2, 3, and 5]

   Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.

9. Alterations in Genes, Proteins, and RNAs Relevant to the Notch Signaling Pathway, to TNBC Biology, and to Sensitivity/Resistance to PF-03084014 in Tumor Specimens and Peripheral Blood. [Day 1 of Cycle 1, 2, 3, and 5]

   Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.

10. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [2 years]

    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. 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. Treatment-emergent AEs were defined as all deaths, regardless of cause, from treatment start until 28 days after the last dose and non-fatal events occurring after treatment start regardless of cause, up until 28 days after the last dose or until start of new anti-cancer treatment, whichever was first.

11. Number of Participants With Treatment-Emergent AEs by CTCAE Grade [2 years]

    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

12. Number of Participants With Laboratory Test (Hematology) Abnormalities [Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.]

    Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.

13. Number of Participants With Laboratory Test (Chemistry) Abnormalities [Day 1 and Day 15 of Cycles 1, 2, 3, 4, 5, and subsequent cycles up to Cycle 8 and Day 8 of Cycle 1]

    Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities

14. Number of Participants With Laboratory Test (Urinalysis) Abnormalities [Day 1 of Cycle 1]

    Number of participants with CTCAE version 4.03 grade 1 to 4 urinalysis test abnormalities for urine protein.

15. Number of Notch Genomic Alterations in Participants With NA+ mTNBC [2 years]

    Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histological or cytological diagnosis of triple negative breast cancer (TNBC) with evidence of a) metastatic or b) locally recurrent advanced disease that is not amenable to resection or radiotherapy with curative intent.

• Availability of an original diagnostic tumor tissue or the most recent metastatic tumor biopsies (archival biopsy or de novo biopsy) and a peripheral blood sample for Notch receptors genomic profiling

Exclusion Criteria:

• Known brain metastases.

• Prior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Institute	Stanford	California	United States	94305
2	Stanford Hospital and Clinics	Stanford	California	United States	94305
3	Stanford Women's Cancer Center	Stanford	California	United States	94305
4	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
5	University of Chicago Medical Center	Chicago	Illinois	United States	60637
6	University of Chicago Comprehensive Cancer Center at Silver Cross Hospital	New Lenox	Illinois	United States	60451
7	Midwestern Regional Medical Center	Zion	Illinois	United States	60099
8	Brigham and Women's Hospital (BWH)	Boston	Massachusetts	United States	02115
9	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts	United States	02215
10	Memorial Sloan Kettering Cancer Center Basking Ridge	Basking Ridge	New Jersey	United States	07920
11	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey	United States	07652
12	Valley Medical Group	Paramus	New Jersey	United States	07652
13	Valley Medical Group	Westwood	New Jersey	United States	07675
14	Memorial Sloan Kettering Cancer Center Commack	Commack	New York	United States	11725
15	Memorial Sloan Kettering Cancer Center West Harrison	Harrison	New York	United States	10604
16	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
17	Memorial Sloan Kettering Cancer Center Rockville Centre	Rockville Centre	New York	United States	11570
18	Memorial Sloan Kettering Cancer Center Sleepy Hollow	Sleepy Hollow	New York	United States	10591
19	Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet	Debrecen		Hungary	4032
20	Presidio Ospedaliero Vito Fazzi	Lecce		Italy	73100
21	Istitutio Europeo di Oncologia	Milan		Italy	20141
22	Vesalius	Krakow		Poland	31108
23	Vesalius Poradnia Onkologiczna i Hematologiczna	Krakow		Poland	31216
24	Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego	Poznan		Poland	60-569
25	Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)	A Coruna		Spain	15006
26	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
27	Hospital Clinic de Barcelona	Barcelona		Spain	08036
28	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
29	Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)	Barcelona		Spain	08908
30	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
31	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
32	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
33	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
34	Beatson West of Scotland Cancer Centre	Glasgow	Scotland	United Kingdom	G12 0YN
35	Ross Hall Hospital	Glasgow	Scotland	United Kingdom	G52 3NQ
36	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SW3 6JJ
37	The Royal Marsden NHS Foundation Trust	Surrey		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Pfizer

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: NCT02299635
• Other Study ID Numbers: A8641020; 2014-002286-30
• First Posted: Nov 24, 2014
• Last Update Posted: Jan 8, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: PF-03084014; Notch Alterations
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Period Title: Overall Study
STARTED	19
COMPLETED	0
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (12.1)
Sex: Female, Male (Count of Participants)
Female	19 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+)
Description	OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis less than [<]10 millimeter [mm]). PR: Greater than or equal to (>=)30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.
Time Frame	Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

2. Secondary Outcome

Title	OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-)
Description	OR status based on assessment of confirmed CR or confirmed PR according to RECIST 1.1. CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis <10 mm). PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.
Time Frame	Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

3. Secondary Outcome

Title	Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC
Description	The period from study entry until disease progression, death, whichever occurred first as per RECIST version 1.1.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

4. Secondary Outcome

Title	Duration of Response (DR) in Participants With NA+ or NA mTNBC
Description	Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated for the subgroup of patients with a confirmed objective tumor response. Objective Progression (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

5. Secondary Outcome

Title	One-Year Survival Probability in Participants With NA+ or NA mTNBC
Description	Overall survival (OS) status (alive or not) at 1 year after study entry. The the survival probability at 1 year was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

6. Secondary Outcome

Title	Overall Survival (OS) in Participants With NA+ or NA mTNBC
Description	OS was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

7. Secondary Outcome

Title	Type of Notch Genomic Alterations in Participants With NA+ mTNBC
Description	Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

8. Secondary Outcome

Title	Pre-dose Serum Concentration (Ctrough) for PF-03084014
Time Frame	Day 1 of Cycle 1, 2, 3, and 5

Outcome Measure Data

Analysis Population Description

Due to study termination, no PK analyses were performed for this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

9. Secondary Outcome

Title	Pharmacodynamic (PD) Effects of PF-03084014 in Tumor Specimens and Peripheral Blood
Description	Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.
Time Frame	Day 1 of Cycle 1, 2, 3, and 5

Outcome Measure Data

Analysis Population Description

Due to study termination, no PD analyses were performed for this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

10. Secondary Outcome

Title	Alterations in Genes, Proteins, and RNAs Relevant to the Notch Signaling Pathway, to TNBC Biology, and to Sensitivity/Resistance to PF-03084014 in Tumor Specimens and Peripheral Blood.
Description	Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.
Time Frame	Day 1 of Cycle 1, 2, 3, and 5

Outcome Measure Data

Analysis Population Description

Due to study termination, no PD analyses were performed for this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

11. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. 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. Treatment-emergent AEs were defined as all deaths, regardless of cause, from treatment start until 28 days after the last dose and non-fatal events occurring after treatment start regardless of cause, up until 28 days after the last dose or until start of new anti-cancer treatment, whichever was first.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	19
Number of Participants with AEs	18 94.7%
Number of Participants with SAEs	6 31.6%

12. Secondary Outcome

Title	Number of Participants With Treatment-Emergent AEs by CTCAE Grade
Description	An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	19
Any AEs, Grade 1	1 5.3%
Any AEs, Grade 2	5 26.3%
Any AEs, Grade 3	9 47.4%
Any AEs, Grade 4	1 5.3%
Any AEs, Grade 5	2 10.5%

13. Secondary Outcome

Title	Number of Participants With Laboratory Test (Hematology) Abnormalities
Description	Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.
Time Frame	Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	19
Anemia	12 63.2%
Lymphocyte count increased	0 0%
Lymphopenia	11 57.9%
Neutrophils (absolute)	0 0%
Platelets	3 15.8%
White blood cells	4 21.1%

14. Secondary Outcome

Title	Number of Participants With Laboratory Test (Chemistry) Abnormalities
Description	Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities
Time Frame	Day 1 and Day 15 of Cycles 1, 2, 3, 4, 5, and subsequent cycles up to Cycle 8 and Day 8 of Cycle 1

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	19
Alanine aminotransferase	5 26.3%
Alkaline phosphatase	6 31.6%
Aspartate aminotransferase	9 47.4%
Bilirubin (total)	1 5.3%
Creatine kinase	1 5.3%
Creatinine	13 68.4%
Gamma glutamyl transferase	1 5.3%
Hypercalcemia	3 15.8%
Hyperglycemia	13 68.4%
Hyperkalemia	3 15.8%
Hypermagnesemia	1 5.3%
Hypernatremia	0 0%
Hypoalbuminemia	8 42.1%
Hypocalcemia	4 21.1%
Hypoglycemia	1 5.3%
Hypokalemia	5 26.3%
Hypomagnesemia	3 15.8%
Hyponatremia	6 31.6%
Hypophosphatemia	14 73.7%

15. Secondary Outcome

Title	Number of Participants With Laboratory Test (Urinalysis) Abnormalities
Description	Number of participants with CTCAE version 4.03 grade 1 to 4 urinalysis test abnormalities for urine protein.
Time Frame	Day 1 of Cycle 1

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	19
Number [participants]	2 10.5%

16. Secondary Outcome

Title	Number of Notch Genomic Alterations in Participants With NA+ mTNBC
Description	Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected due to early termination of this study.

Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Measure Participants	0

Adverse Events

Time Frame	2 years
Arm/Group Title	PF-03084014
Arm/Group Description	PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
All Cause Mortality
	PF-03084014
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PF-03084014
	Affected / at Risk (%)	# Events
Total	6/19 (31.6%)
General disorders
Disease progression	1/19 (5.3%)
Pyrexia	1/19 (5.3%)
Infections and infestations
Lung infection	1/19 (5.3%)
Metabolism and nutrition disorders
Hypophosphataemia	1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma	1/19 (5.3%)
Psychiatric disorders
Confusional state	2/19 (10.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	PF-03084014
	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)
Cardiac disorders
Angina pectoris	1/19 (5.3%)
Ear and labyrinth disorders
Vertigo	1/19 (5.3%)
Eye disorders
Eye discharge	1/19 (5.3%)
Photopsia	1/19 (5.3%)
Vitreous floaters	1/19 (5.3%)
Gastrointestinal disorders
Abdominal pain	1/19 (5.3%)
Abdominal pain upper	1/19 (5.3%)
Diarrhoea	11/19 (57.9%)
Dry mouth	2/19 (10.5%)
Dyspepsia	3/19 (15.8%)
Nausea	8/19 (42.1%)
Oral pain	1/19 (5.3%)
Stomatitis	2/19 (10.5%)
Vomiting	7/19 (36.8%)
General disorders
Asthenia	1/19 (5.3%)
Chest pain	2/19 (10.5%)
Fatigue	8/19 (42.1%)
Mucosal inflammation	3/19 (15.8%)
Oedema peripheral	1/19 (5.3%)
Pyrexia	5/19 (26.3%)
Infections and infestations
Conjunctivitis	3/19 (15.8%)
Gastroenteritis viral	1/19 (5.3%)
Nasopharyngitis	1/19 (5.3%)
Pharyngitis	1/19 (5.3%)
Respiratory tract infection	1/19 (5.3%)
Urinary tract infection	2/19 (10.5%)
Investigations
Alanine aminotransferase increased	1/19 (5.3%)
Aspartate aminotransferase increased	3/19 (15.8%)
Blood alkaline phosphatase increased	1/19 (5.3%)
Blood chloride decreased	1/19 (5.3%)
Blood creatinine increased	1/19 (5.3%)
Carbon dioxide increased	2/19 (10.5%)
Electrocardiogram QT prolonged	1/19 (5.3%)
Glomerular filtration rate decreased	1/19 (5.3%)
Protein total increased	1/19 (5.3%)
Transaminases increased	1/19 (5.3%)
Weight decreased	2/19 (10.5%)
Metabolism and nutrition disorders
Decreased appetite	2/19 (10.5%)
Hypercalcaemia	1/19 (5.3%)
Hyperglycaemia	1/19 (5.3%)
Hypoalbuminaemia	1/19 (5.3%)
Hypocalcaemia	1/19 (5.3%)
Hypokalaemia	3/19 (15.8%)
Hypophosphataemia	7/19 (36.8%)
Hypouricaemia	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Bone pain	1/19 (5.3%)
Flank pain	1/19 (5.3%)
Muscular weakness	1/19 (5.3%)
Musculoskeletal chest pain	1/19 (5.3%)
Myalgia	2/19 (10.5%)
Neck pain	1/19 (5.3%)
Pain in extremity	1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour exudation	1/19 (5.3%)
Tumour haemorrhage	1/19 (5.3%)
Tumour pain	1/19 (5.3%)
Nervous system disorders
Balance disorder	1/19 (5.3%)
Dizziness	1/19 (5.3%)
Dysgeusia	2/19 (10.5%)
Headache	1/19 (5.3%)
Lethargy	2/19 (10.5%)
Peripheral motor neuropathy	1/19 (5.3%)
Psychiatric disorders
Anxiety	1/19 (5.3%)
Depression	1/19 (5.3%)
Renal and urinary disorders
Haematuria	1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	5/19 (26.3%)
Nasal congestion	1/19 (5.3%)
Productive cough	1/19 (5.3%)
Upper respiratory tract inflammation	1/19 (5.3%)
Skin and subcutaneous tissue disorders
Nail dystrophy	1/19 (5.3%)
Palmar-plantar erythrodysaesthesia syndrome	1/19 (5.3%)
Rash	3/19 (15.8%)
Rash macular	1/19 (5.3%)
Urticaria	1/19 (5.3%)

Limitations/Caveats

This study was terminated prematurely based on project re-prioritization by the Sponsor and was not due to any safety concerns or regulatory actions.

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.