A Phase 2 Trial of Standard Chemotherapy, With or Without BSI-201, in Patients With Triple Negative Metastatic Breast Cancer

December 21, 2012 updated by: Sanofi

A Phase 2, Multi-center, Open-Label, Randomized Trial of Gemcitabine/ Carboplatin, With or Without BSI-201, in Patients With ER, PR and HER2-negative Metastatic Breast Cancer

The purpose of this clinical trial was to determine whether combining iniparib (BSI-201) with standard chemotherapy in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer patients improve clinical benefit compared to treatment with standard chemotherapy alone.

Based on data generated by BiPar/Sanofi, it was 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients were treated until disease progression, unacceptable toxicity, Investigator's decision to discontinue, or withdrawal of consent. After treatment discontinuation, all patients were evaluated every 90 days after last dose of gemcitabine/carboplatin with or without iniparib, for up to 3 years or death or end of study, which ever occurred first.

Study Type

Interventional

Enrollment (Actual)

123

Phase

  • Phase 2

Expanded Access

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States
        • Research Site
    • Colorado
      • Denver, Colorado, United States
        • Research Site
    • Connecticut
      • Torrington, Connecticut, United States
        • Research Site
    • Florida
      • Ocoee, Florida, United States
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States
        • Research Site
    • Kansas
      • Overland Park, Kansas, United States
        • Research Site
    • Nevada
      • Henderson, Nevada, United States
        • Research Site
    • New Hampshire
      • Hooksett, New Hampshire, United States
        • Research Site
    • North Carolina
      • Raleigh, North Carolina, United States
        • Research Site
    • Texas
      • Bedford, Texas, United States
        • Research Site
      • Dallas, Texas, United States
        • Research Site
      • El Paso, Texas, United States
        • Research Site
      • Fort Worth, Texas, United States
        • Research Site
      • Houston, Texas, United States
        • Research Site
      • Tyler, Texas, United States
        • Research Site
    • Virginia
      • Fairfax, Virginia, United States
        • Research Site
    • Washington
      • Vancouver, Washington, United States
        • Research Site
      • Yakima, Washington, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • At least 18 years of age;
  • Metastatic breast cancer (Stage IV) with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria;
  • 0-2 prior chemotherapy regimens in the metastatic setting;
  • Histologically documented (either primary or metastatic site) breast cancer that was ER-negative, PR-negative, and HER-2 nonoverexpressing by immunohistochemistry (0,1) or non-gene amplification by fluorescence in situ hybridization (FISH);
  • Completion of prior chemotherapy at least 2 weeks prior to trial entry and recovery from toxicity of prior chemotherapy;
  • Radiation therapy must have been completed at least 2 weeks prior to trial entry, and radiated lesions may not have served as measurable disease;
  • Patient may have had central nervous system (CNS) metastases if he/she did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
  • Adequate organ function defined as: absolute neutrophil count (ANC)≥1,500/mm3, platelets ≥100,000/mm3, creatinine clearance >50mL/min, ALT and AST <2.5 x upper limit of normal (ULN) (or <5 x ULN in case of liver metastases); total bilirubin <1.5 mg/dL.
  • Tissue block (primary or metastatic) available for PARP and PG studies was recommended, although its absence did not exclude subjects from participating;
  • Woman of child bearing potential must have had documented negative pregnancy test within two weeks of trial entry and agreed to acceptable birth control during the duration of the trial therapy;
  • Signed, IRB approved written informed consent.

Exclusion Criteria:

  • Lesions identifiable only by positron emission tomography (PET);
  • Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib;
  • Major medical conditions that might have affected trial participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection);
  • Significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy that was either symptomatic or asymptomatic but with decreased ejection fraction <45%;
  • Other significant comorbid condition which the investigator felt might compromise effective and safe participation in the trial;
  • Patient enrolled in another investigational device or drug trial, or was receiving other investigational agents;
  • Concurrent or prior (within 7 days of trial day 1) anticoagulation therapy (low dose for port maintenance allowed);
  • Concurrent radiation therapy was not permitted throughout the course of the trial;
  • Inability to comply with the requirements of the trial;
  • Pregnant or lactating woman;
  • Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Arm G/C
Standard chemotherapy with gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)
Drug: gemcitabine/carboplatin
Gemcitabine and carboplatin administered according to instructions in the package inserts.
EXPERIMENTAL: Arm G/C/I
Standard chemotherapy with gemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s)
Drug: gemcitabine/carboplatin
Gemcitabine and carboplatin administered according to instructions in the package inserts.
Drug: iniparib

Body weight adjusted dose

1 hour intravenous infusion

Other Names:
  • BSI-201
  • SAR240550

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical benefit rate
Time Frame: until cut-off date established so that all patients were evaluable for primary outcome measure
Clinical benefit rate was defined as the percentage of patients with complete response, partial response or stable disease ≥6 months.
until cut-off date established so that all patients were evaluable for primary outcome measure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: until cut-off date established so that all patients were evaluable for primary outcome measure
Objective response rate was defined as the percentage of patients with confirmed partial response or complete response
until cut-off date established so that all patients were evaluable for primary outcome measure
Progression-free survival
Time Frame: until cut-off date established so that all patients were evaluable for primary outcome measure
Progression-free survival was defined as the time interval from the date of randomization to the date of disease progression or the date of death due to any cause, whichever came first.
until cut-off date established so that all patients were evaluable for primary outcome measure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Collaborators

BiPar Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

June 1, 2010

Study Registration Dates

First Submitted

October 4, 2007

First Submitted That Met QC Criteria

October 5, 2007

First Posted (ESTIMATE)

October 8, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

December 28, 2012

Last Update Submitted That Met QC Criteria

December 21, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TCD11485
  • 20070102 (OTHER: BiPar)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on gemcitabine/carboplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cambodia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe