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-)
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Tablet, 10 mg, twice a day.
Tablet, 50 mg, twice a day
Tablet, 100 mg, twice a day
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.
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.
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.
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.
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.
Time frame: 2 years
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.
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Stanford Cancer Institute
Stanford, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
Stanford Women's Cancer Center
Stanford, California, United States
The University of Chicago Medical Center
Chicago, Illinois, United States
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
Brigham and Women's Hospital (BWH)
Boston, Massachusetts, United States
Dana-Farber Cancer Institute (DFCI)
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
Basking Ridge, New Jersey, United States
...and 27 more locations
Time frame: 2 years
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.
Time frame: 1 year
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.
Time frame: 2 years
Type of Notch Genomic Alterations in Participants With NA+ mTNBC
Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Time frame: 2 years
Pre-dose Serum Concentration (Ctrough) for PF-03084014
Time frame: Day 1 of Cycle 1, 2, 3, and 5
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.
Time frame: 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.
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
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.
Time frame: 2 years
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.
Time frame: 2 years
Number of Participants With Laboratory Test (Hematology) Abnormalities
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.
Number of Participants With Laboratory Test (Chemistry) Abnormalities
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
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.
Time frame: Day 1 of Cycle 1
Number of Notch Genomic Alterations in Participants With NA+ mTNBC
Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Time frame: 2 years