A Phase 3, Multi-Center, Open-Label, Randomized Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer
Overview
- Phase
- Phase 3
- Intervention
- gemcitabine/carboplatin
- Conditions
- Breast Cancer
- Sponsor
- Sanofi
- Enrollment
- 519
- Locations
- 3
- Primary Endpoint
- progression free survival
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The goal of this study was to determine the effect on overall survival and progression free survival by adding iniparib (BSI-201/SAR240550) to the combination of gemcitabine/carboplatin in adult patients with triple negative breast cancer (estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative).
Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the poly (ADP-ribose) polymerase (PARP) inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.
Detailed Description
Participants were treated for 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. After treatment discontinuation, participants were followed until end of study or death or receipt of new anticancer therapy, whichever was first.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically documented breast cancer (either primary or metastatic site) that is ER-negative, PR-negative, and HER2 non-overexpressing by immunohistochemistry (0, 1) or fluorescence in situ hybridization (FISH).
- •Triple-negative tumors were defined by the following criteria:
- •HER2-non-overexpressing: FISH-negative (defined by ratio \<2.2) or, immunohistochemical (IHC) 0, IHC 1+ or, IHC 2+ or IHC 3+ and FISH-negative.
- •ER- and PR-negative: \<10% tumor staining by immunohistochemistry (IHC).
- •Never having received chemotherapy for metastatic disease or, having received 1 or 2 prior chemotherapy regimens in the metastatic setting (Prior adjuvant/neoadjuvant therapy was allowed);
- •Metastatic breast cancer (Stage IV) with measurable disease by RECIST 1.1 criteria;
- •Female, ≥18 years of age;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- •Organ and marrow function as follows: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/dL, hemoglobin ≥9 g/dL, bilirubin ≤1.5 mg/dL, serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement;
- •Radiation therapy completed at least 14 days before study dosing on day 1; radiated lesions may not have served as measurable disease;
Exclusion Criteria
- •Systemic anticancer therapy within 14 days of the first dose of study drug;
- •Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib
- •Had not recovered to grade ≤1 from adverse events (AEs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 or to within 10% of baseline values due to investigational drugs or other medications administered more than 30 days prior to study enrollment;
- •Major medical conditions that might have affected study participation (e.g. uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease);
- •Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation was acceptable;
- •Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention;
- •Pregnancy or breastfeeding;
- •Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
Arms & Interventions
Arm G/C
gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)
Intervention: gemcitabine/carboplatin
Arm G/C/I
gemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s)
Intervention: gemcitabine/carboplatin
Arm G/C/I
gemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s)
Intervention: Iniparib
Outcomes
Primary Outcomes
progression free survival
Time Frame: until cut-off date established from deaths rate
Progression free survival was defined as the time interval from the date of randomization to the date of first disease progression (as assessed by Independent Radiologic Review (IRR) based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria), or the date of death due to any cause, whichever occurred first. In the absence disease progression or death, the participant was censored at the date of the last valid tumor assessment performed before the cut-off date.
Overall survival
Time Frame: until cut-off date established from deaths rate
Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, participant was censored at the last date he/she was known to be alive, or at the cut-off date, whichever was earlier.
Secondary Outcomes
- Objective response rate(until treatment discontinuation (assessment at the end of cycle 2 then every other cycle))
- Best overall response(until treatment discontinuation (assessment at the end of cycle 2 then every other cycle))