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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00540358

Collaborator

BiPar Sciences (Industry)

123

Enrollment

Locations

Arms

Duration (Months)

6.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Design

Study Type:

Interventional

Actual Enrollment :

123 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Clinical benefit rate [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.

Secondary Outcome Measures

Objective response rate [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Denver	Colorado	United States
3	Research Site	Torrington	Connecticut	United States
4	Research Site	Ocoee	Florida	United States
5	Research Site	Indianapolis	Indiana	United States
6	Research Site	Overland Park	Kansas	United States
7	Research Site	Henderson	Nevada	United States
8	Research Site	Hooksett	New Hampshire	United States
9	Research Site	Raleigh	North Carolina	United States
10	Research Site	Bedford	Texas	United States
11	Research Site	Dallas	Texas	United States
12	Research Site	El Paso	Texas	United States
13	Research Site	Fort Worth	Texas	United States
14	Research Site	Houston	Texas	United States
15	Research Site	Tyler	Texas	United States
16	Research Site	Fairfax	Virginia	United States
17	Research Site	Vancouver	Washington	United States
18	Research Site	Yakima	Washington	United States