Back to resultsA Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations
Primary Purpose
Triple Negative Breast Neoplasms
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-03084014
PF-03084014
PF-03084014
Sponsored by
About this trial
This is an interventional treatment trial for Triple Negative Breast Neoplasms focused on measuring PF-03084014, Notch Alterations
Eligibility Criteria
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.
Sites / Locations
- Stanford Cancer Institute
- Stanford Hospital and Clinics
- Stanford Women's Cancer Center
- The University of Chicago Medical Center
- University of Chicago Medical Center
- University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
- Midwestern Regional Medical Center
- Brigham and Women's Hospital (BWH)
- Dana-Farber Cancer Institute (DFCI)
- Memorial Sloan Kettering Cancer Center Basking Ridge
- The Valley Hospital - Luckow Pavilion
- Valley Medical Group
- Valley Medical Group
- Memorial Sloan Kettering Cancer Center Commack
- Memorial Sloan Kettering Cancer Center West Harrison
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Cancer Center Rockville Centre
- Memorial Sloan Kettering Cancer Center Sleepy Hollow
- Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet
- Presidio Ospedaliero Vito Fazzi
- Istitutio Europeo di Oncologia
- Vesalius
- Vesalius Poradnia Onkologiczna i Hematologiczna
- Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego
- Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)
- Hospital Universitari Vall d'Hebron
- Hospital Clinic de Barcelona
- Hospital de la Santa Creu i Sant Pau
- Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)
- Hospital General Universitario Gregorio Maranon
- Hospital Universitario 12 de Octubre
- Hospital Universitario Virgen del Rocio
- Hospital Clínico Universitario de Valencia
- Beatson West of Scotland Cancer Centre
- Ross Hall Hospital
- The Royal Marsden NHS Foundation Trust
- The Royal Marsden NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-03084014
Arm Description
PF-03084014 will be administered orally, continuously, twice daily at 150 mg, but the dose can be reduced to 100 mg or 80 mg.
Outcomes
Primary Outcome Measures
Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+)
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
OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-)
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.
Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC
The period from study entry until disease progression, death, whichever occurred first as per RECIST version 1.1.
Duration of Response (DR) in Participants With NA+ or NA mTNBC
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.
One-Year Survival Probability in Participants With NA+ or NA mTNBC
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.
Overall Survival (OS) in Participants With NA+ or NA mTNBC
OS was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Type of Notch Genomic Alterations in Participants With NA+ mTNBC
Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Pre-dose Serum Concentration (Ctrough) for PF-03084014
Pharmacodynamic (PD) Effects of PF-03084014 in Tumor Specimens and Peripheral Blood
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.
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.
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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
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.
Number of Participants With Treatment-Emergent AEs by CTCAE Grade
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.
Number of Participants With Laboratory Test (Hematology) Abnormalities
Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities
Number of Participants With Laboratory Test (Urinalysis) Abnormalities
Number of participants with CTCAE version 4.03 grade 1 to 4 urinalysis test abnormalities for urine protein.
Number of Notch Genomic Alterations in Participants With NA+ mTNBC
Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02299635
Brief Title
A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated on June 24th, 2015 due to change in strategy of PF-03084014 development. There were no safety/efficacy concerns behind the decision.
Study Start Date
February 3, 2015 (Actual)
Primary Completion Date
January 14, 2016 (Actual)
Study Completion Date
January 14, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. 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-)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Neoplasms
Keywords
PF-03084014, Notch Alterations
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-03084014
Arm Type
Experimental
Arm Description
PF-03084014 will be administered orally, continuously, twice daily at 150 mg, but the dose can be reduced to 100 mg or 80 mg.
Intervention Type
Drug
Intervention Name(s)
PF-03084014
Intervention Description
Tablet, 10 mg, twice a day.
Intervention Type
Drug
Intervention Name(s)
PF-03084014
Intervention Description
Tablet, 50 mg, twice a day
Intervention Type
Drug
Intervention Name(s)
PF-03084014
Intervention Description
Tablet, 100 mg, twice a day
Primary Outcome Measure Information:
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.
Secondary Outcome Measure Information:
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.
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
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
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
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
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
Title
Pre-dose Serum Concentration (Ctrough) for PF-03084014
Time Frame
Day 1 of Cycle 1, 2, 3, and 5
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
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
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
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
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.
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
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
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
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Stanford Women's Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
City
New Lenox
State/Province
Illinois
ZIP/Postal Code
60451
Country
United States
Facility Name
Midwestern Regional Medical Center
City
Zion
State/Province
Illinois
ZIP/Postal Code
60099
Country
United States
Facility Name
Brigham and Women's Hospital (BWH)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute (DFCI)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
The Valley Hospital - Luckow Pavilion
City
Paramus
State/Province
New Jersey
ZIP/Postal Code
07652
Country
United States
Facility Name
Valley Medical Group
City
Paramus
State/Province
New Jersey
ZIP/Postal Code
07652
Country
United States
Facility Name
Valley Medical Group
City
Westwood
State/Province
New Jersey
ZIP/Postal Code
07675
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center West Harrison
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Rockville Centre
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Sleepy Hollow
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
Country
United States
Facility Name
Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Presidio Ospedaliero Vito Fazzi
City
Lecce
ZIP/Postal Code
73100
Country
Italy
Facility Name
Istitutio Europeo di Oncologia
City
Milan
ZIP/Postal Code
20141
Country
Italy
Facility Name
Vesalius
City
Krakow
ZIP/Postal Code
31108
Country
Poland
Facility Name
Vesalius Poradnia Onkologiczna i Hematologiczna
City
Krakow
ZIP/Postal Code
31216
Country
Poland
Facility Name
Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
Facility Name
Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)
City
A Coruna
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital General Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Ross Hall Hospital
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G52 3NQ
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A8641020&StudyName=A%20Study%20Evaluating%20PF-03084014%20In%20Patients%20With%20Advanced%20Breast%0ACancer%20With%20Or%20Without%20Notch%20Alterations
Description
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Learn more about this trial
A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations
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