A Study Evaluating BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors

A Phase 1B, Open-Label, Dose Escalation Study Evaluating the Safety of BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors

The purpose of the study is to assess the safety and establish the maximum tolerated dose (MTD) of the combination of BSI-201 with chemotherapeutic regimens in adult subjects with histologically or cytologically documented advanced solid tumors.

Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the 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.

Inclusion Criteria:

• ≥ 18 years old with a histologically or cytologically documented, advanced solid tumor
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without granulocyte colony-stimulating factor [G-CSF] support within 2 weeks of study day 1); platelet count ≥ 100.0 x 10^9/L (without transfusion within 2 weeks of study day 1); and hemoglobin ≥ 9.0 g/dL (erythropoietic agents allowed)
• At least a 14-day period from end of last dose of chemotherapy received
• Any prior toxicity from prior chemotherapeutic treatment recovered to ≤ grade 1

Exclusion Criteria:

• Subject enrolled in another investigational device or drug trial, or is receiving other investigational agents
• Hematological malignancies
• Symptomatic or untreated brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids.
• History of seizure disorder
• Myocardial infarction (MI) within 6 months of study day 1, unstable angina, congestive heart failure (CHF) with New York Heart Association (NYHA) > class II, or uncontrolled hypertension
• Concurrent or prior (within 7 days of study day 1) anticoagulation therapy (low dose for port maintenance allowed)
• Specified concomitant medications
• Serum creatinine > 1.5 x upper limit of normal (ULN)
• Elevated liver enzymes (AST/ALT) > 2.5 x ULN, or > 5.0 x ULN if secondary to liver metastases; alkaline phosphatase > 2.5 x ULN or > 5.0 x ULN if secondary to liver or bone metastases; total bilirubin > 1.5 x ULN
• Radiation therapy within 14 days of study day 1
• Antibody therapy for the treatment of an underlying malignancy within 14 days of study day 1
• Concurrent radiation therapy is not permitted throughout the course of the study