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

NCT ID: NCT00540358

Last Updated: 2012-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

123 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2010-06-30

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Keywords

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Triple negative breast cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm G/C

Standard chemotherapy with gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)

Group Type ACTIVE_COMPARATOR

gemcitabine/carboplatin

Intervention Type DRUG

Gemcitabine and carboplatin administered according to instructions in the package inserts.

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)

Group Type EXPERIMENTAL

gemcitabine/carboplatin

Intervention Type DRUG

Gemcitabine and carboplatin administered according to instructions in the package inserts.

iniparib

Intervention Type DRUG

Body weight adjusted dose

1 hour intravenous infusion

Interventions

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gemcitabine/carboplatin

Gemcitabine and carboplatin administered according to instructions in the package inserts.

Intervention Type DRUG

iniparib

Body weight adjusted dose

1 hour intravenous infusion

Intervention Type DRUG

Other Intervention Names

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BSI-201 SAR240550

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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BiPar Sciences

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Research Site

Birmingham, Alabama, United States

Site Status

Research Site

Denver, Colorado, United States

Site Status

Research Site

Torrington, Connecticut, United States

Site Status

Research Site

Ocoee, Florida, United States

Site Status

Research Site

Indianapolis, Indiana, United States

Site Status

Research Site

Overland Park, Kansas, United States

Site Status

Research Site

Henderson, Nevada, United States

Site Status

Research Site

Hooksett, New Hampshire, United States

Site Status

Research Site

Raleigh, North Carolina, United States

Site Status

Research Site

Bedford, Texas, United States

Site Status

Research Site

Dallas, Texas, United States

Site Status

Research Site

El Paso, Texas, United States

Site Status

Research Site

Fort Worth, Texas, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Tyler, Texas, United States

Site Status

Research Site

Fairfax, Virginia, United States

Site Status

Research Site

Vancouver, Washington, United States

Site Status

Research Site

Yakima, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 21208101 (View on PubMed)

Other Identifiers

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20070102

Identifier Type: OTHER

Identifier Source: secondary_id

TCD11485

Identifier Type: -

Identifier Source: org_study_id