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

This study has been completed.
Sponsor:
Collaborator:
BiPar Sciences
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00540358
First received: October 4, 2007
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: gemcitabine/carboplatin
Drug: iniparib
Phase 2

Access to an investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Clinical benefit rate [ Time Frame: until cut-off date established so that all patients were evaluable for primary outcome measure ] [ Designated as safety issue: No ]
    Clinical benefit rate was defined as the percentage of patients with complete response, partial response or stable disease ≥6 months.


Secondary Outcome Measures:
  • Objective response rate [ Time Frame: until cut-off date established so that all patients were evaluable for primary outcome measure ] [ Designated as safety issue: No ]
    Objective response rate was defined as the percentage of patients with confirmed partial response or complete response

  • Progression-free survival [ Time Frame: until cut-off date established so that all patients were evaluable for primary outcome measure ] [ Designated as safety issue: No ]
    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.


Enrollment: 123
Study Start Date: October 2007
Study Completion Date: June 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00540358

Locations
United States, Alabama
Research Site
Birmingham, Alabama, United States
United States, Colorado
Research Site
Denver, Colorado, United States
United States, Connecticut
Research Site
Torrington, Connecticut, United States
United States, Florida
Research Site
Ocoee, Florida, United States
United States, Indiana
Research Site
Indianapolis, Indiana, United States
United States, Kansas
Research Site
Overland Park, Kansas, United States
United States, Nevada
Research Site
Henderson, Nevada, United States
United States, New Hampshire
Research Site
Hooksett, New Hampshire, United States
United States, North Carolina
Research Site
Raleigh, North Carolina, United States
United States, Texas
Research Site
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
United States, Virginia
Research Site
Fairfax, Virginia, United States
United States, Washington
Research Site
Vancouver, Washington, United States
Research Site
Yakima, Washington, United States
Sponsors and Collaborators
Sanofi
BiPar Sciences
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00540358     History of Changes
Other Study ID Numbers: TCD11485, 20070102
Study First Received: October 4, 2007
Last Updated: December 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Triple negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 14, 2014