A Phase 3, Multi-Center Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer

• Status: Completed
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Carboplatin; Gemcitabine; Iniparib

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;

• Central nervous system metastases allowed if subject did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;

• For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy;

• Tissue block (primary or metastatic) or readily available fresh frozen tumor tissue for PARP expression and other pharmacogenomic studies recommended (although its absence will not exclude subjects from participating);

• No other diagnosis of malignancy (with exception of non melanoma skin cancer or a malignancy diagnosed ≥5 years ago);

• Obtained informed consent;

• Capability to understand and comply with the protocol and signed informed consent document.

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.