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.

Study Overview

• Status: Completed
• Conditions: Tumors
• Intervention / Treatment: Drug: bsi-201 + topotecan; Drug: bsi-201 + temozolomide; Drug: bsi-201 + gemcitabine; Drug: bsi-201 + carboplatin/paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States
      • Research Site
  • Michigan
    • Detroit, Michigan, United States
      • Research Site
  • New York
    • New York City, New York, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Texas
    • Houston, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; BSI-201 + topotecan	Drug: bsi-201 + topotecan; 21 day cycle
Experimental: 2; BSI-201 + temozolomide	Drug: bsi-201 + temozolomide; 28 day cycle
Experimental: 3; bsi-201 + gemcitabine	Drug: bsi-201 + gemcitabine; 28 day cycle
Experimental: 4; bsi-201 + carboplatin/paclitaxel	Drug: bsi-201 + carboplatin/paclitaxel; 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety and efficacy	ongoing
Response rate (CR + PR)	every 2 cycles

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: January 12, 2007
• First Submitted That Met QC Criteria: January 16, 2007
• First Posted (Estimate): January 17, 2007

Study Record Updates

• Last Update Posted (Estimate): June 10, 2016
• Last Update Submitted That Met QC Criteria: June 9, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Topoisomerase I Inhibitors; Gemcitabine; Carboplatin; Paclitaxel; Temozolomide; Topotecan; Iniparib
• Other Study ID Numbers: TCD11484; 20060102 (BiPar)