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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00540358
Recruitment Status : Completed
First Posted : October 8, 2007
Last Update Posted : December 28, 2012
BiPar Sciences
Information provided by (Responsible Party):

Tracking Information
First Submitted Date  ICMJE October 4, 2007
First Posted Date  ICMJE October 8, 2007
Last Update Posted Date December 28, 2012
Study Start Date  ICMJE October 2007
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2012)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2012)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Phase 2 Trial of Standard Chemotherapy, With or Without BSI-201, in Patients With Triple Negative Metastatic Breast Cancer
Official Title  ICMJE 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
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: Arm G/C
    Standard chemotherapy with gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)
    Intervention: Drug: gemcitabine/carboplatin
  • 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
    • Drug: iniparib
Publications * O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011 Jan 20;364(3):205-14. doi: 10.1056/NEJMoa1011418. Epub 2011 Jan 5.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 26, 2011)
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2007)
Actual Study Completion Date  ICMJE June 2010
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00540358
Other Study ID Numbers  ICMJE TCD11485
20070102 ( Other Identifier: BiPar )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE BiPar Sciences
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP