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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00540358
• Other study ID #: TCD11485
• Secondary ID: 20070102
• Status: Completed
• Phase: Phase 2
• First received: October 4, 2007
• Last updated: December 21, 2012
• Start date: October 2007
• Est. completion date: June 2010

Study information

• Verified date: December 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: June 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• gemcitabine/carboplatin
Gemcitabine and carboplatin administered according to instructions in the package inserts.
• iniparib
Body weight adjusted dose 1 hour intravenous infusion

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	BiPar Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical benefit rate	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	No
Secondary	Objective response rate	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	No
Secondary	Progression-free survival	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	No