A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations
- Registration Number
- NCT02299635
- Lead Sponsor
- Pfizer
- 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-)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 19
- 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
- Known brain metastases.
- Prior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description PF-03084014 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
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.
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.
Pre-dose Serum Concentration (Ctrough) for PF-03084014 Day 1 of Cycle 1, 2, 3, and 5 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.
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.
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.
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.
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
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
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.
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.
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.
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
Trial Locations
- Locations (35)
Brigham and Women's Hospital (BWH)
🇺🇸Boston, Massachusetts, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Stanford Women's Cancer Center
🇺🇸Stanford, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
Dana-Farber Cancer Institute (DFCI)
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
The Valley Hospital - Luckow Pavilion
🇺🇸Paramus, New Jersey, United States
Valley Medical Group
🇺🇸Westwood, New Jersey, United States
Memorial Sloan Kettering Cancer Center Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center West Harrison
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center Rockville Centre
🇺🇸Rockville Centre, New York, United States
Memorial Sloan Kettering Cancer Center Sleepy Hollow
🇺🇸Sleepy Hollow, New York, United States
Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet
ðŸ‡ðŸ‡ºDebrecen, Hungary
Istitutio Europeo di Oncologia
🇮🇹Milan, Italy
Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego
🇵🇱Poznan, Poland
Vesalius
🇵🇱Krakow, Poland
Presidio Ospedaliero Vito Fazzi
🇮🇹Lecce, Italy
Vesalius Poradnia Onkologiczna i Hematologiczna
🇵🇱Krakow, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)
🇪🇸A Coruna, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)
🇪🇸Barcelona, Spain
Hospital ClÃnico Universitario de Valencia
🇪🇸Valencia, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Surrey, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Ross Hall Hospital
🇬🇧Glasgow, Scotland, United Kingdom
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain