A Phase 3, Multi-Center Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 3, Multi-Center, Open-Label, Randomized Study 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: NCT00938652
• Other study ID #: EFC11486
• Secondary ID: 20090301U1111-11
• Status: Completed
• Phase: Phase 3
• First received: July 10, 2009
• Last updated: September 13, 2013
• Start date: July 2009
• Est. completion date: February 2012

Study information

• Verified date: September 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The goal of this study was to determine the effect on overall survival and progression free survival by adding iniparib (BSI-201/SAR240550) to the combination of gemcitabine/carboplatin in adult patients with triple negative breast cancer (estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative).

Based on data generated by BiPar/Sanofi, it is 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:

Participants were treated for 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. After treatment discontinuation, participants were followed until end of study or death or receipt of new anticancer therapy, whichever was first.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 519
• Est. completion date: February 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically documented breast cancer (either primary or metastatic site) that is ER-negative, PR-negative, and HER2 non-overexpressing by immunohistochemistry (0, 1) or fluorescence in situ hybridization (FISH).

Triple-negative tumors were defined by the following criteria:

• HER2-non-overexpressing: FISH-negative (defined by ratio <2.2) or, immunohistochemical (IHC) 0, IHC 1+ or, IHC 2+ or IHC 3+ and FISH-negative.

• ER- and PR-negative: <10% tumor staining by immunohistochemistry (IHC).

• Never having received chemotherapy for metastatic disease or, having received 1 or 2 prior chemotherapy regimens in the metastatic setting (Prior adjuvant/neoadjuvant therapy was allowed);

• Metastatic breast cancer (Stage IV) with measurable disease by RECIST 1.1 criteria;

• Female, =18 years of age;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;

• Organ and marrow function as follows: absolute neutrophil count (ANC) =1500/mm3, platelets =100,000/dL, hemoglobin =9 g/dL, bilirubin =1.5 mg/dL, serum creatinine =1.5 mg/dL or creatinine clearance =60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 times the upper limit of normal if no liver involvement or =5 times the upper limit of normal with liver involvement;

• Radiation therapy completed at least 14 days before study dosing on day 1; radiated lesions may not have served as measurable disease;

• Central nervous system metastases allowed if subject did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;

• For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy;

• Tissue block (primary or metastatic) or readily available fresh frozen tumor tissue for PARP expression and other pharmacogenomic studies recommended (although its absence will not exclude subjects from participating);

• No other diagnosis of malignancy (with exception of non melanoma skin cancer or a malignancy diagnosed =5 years ago);

• Obtained informed consent;

• Capability to understand and comply with the protocol and signed informed consent document.

Exclusion Criteria:

• Systemic anticancer therapy within 14 days of the first dose of study drug;

• Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib

• Had not recovered to grade =1 from adverse events (AEs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 or to within 10% of baseline values due to investigational drugs or other medications administered more than 30 days prior to study enrollment;

• Major medical conditions that might have affected study participation (e.g. uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease);

• Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation was acceptable;

• Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention;

• Pregnancy or breastfeeding;

• Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.

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 1000 mg/m2 intravenous infusion (30 ± 10 minutes) Carboplatin AUC 2 intravenous infusion (30 ± 10 minutes or 60 ± 10 minutes)
• Iniparib
Body weight adjusted dose intravenous infusion (60 ± 10 minutes)

Locations

Country	Name	City	State
United States	Research Site	Albany	Georgia
United States	Research Site	Alhambra	California
United States	Research Site	Amsterdam	New York
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Athens	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Augusta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bedford	Texas
United States	Reserach Site	Billings	Montana
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bonita Springs	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Campbell	California
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chevy Chase	Maryland
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Coeur D'alene	Idaho
United States	Research Site	Columbia	Missouri
United States	Reserach Site	Columbia	South Carolina
United States	Research Site	Dallas	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Durham	North Carolina
United States	Reserach Site	Durham	North Carolina
United States	Research Site	East Setauket	New York
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fredericksburg	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Gainesville	Florida
United States	Research Site	Grand Island	Nebraska
United States	Research Site	Grand Junction	Colorado
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Hollywood	Florida
United States	Research Site	Hooksett	New Hampshire
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jackson	Mississippi
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	Kennewick	Washington
United States	Research Site	Lancaster	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Macon	Georgia
United States	Research Site	Marietta	Georgia
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Morristown	New Jersey
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York City	New York
United States	Research Site	Norfolk	Virginia
United States	Research Site	Nothridge	California
United States	Research Site	Ocala	Florida
United States	Research Site	Ocoee	Florida
United States	Research Site	Orange Park	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Overland Park	Kansas
United States	Research Site	Oxnard	California
United States	Research Site	Palo Alto	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pomona	California
United States	Research Site	Port St Lucie	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Redondo Beach	California
United States	Research Site	Richmond	Virginia
United States	Research Site	Roanoke	Virginia
United States	Research Site	Rochester	Minnesota
United States	Research Site	Royal	Michigan
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Francisco	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Santa Fe	New Mexico
United States	Research Site	Santa Maria	California
United States	Research Site	Savannah	Georgia
United States	Research Sites	Seattle	Washington
United States	Research Site	Sedona	Arizona
United States	Research Site	Sparta	New Jersey
United States	Research Site	St Louis	Missouri
United States	Research Site	Suffolk	Virginia
United States	Research Site	Sylmar	California
United States	Research Site	Toledo	Ohio
United States	Research Site	Tyler	Texas
United States	Research Site	Vallejo	California
United States	Research Site	Vancouver	Washington
United States	Research Site	Washington	District of Columbia
United States	Research Site	Westlake Village	California
United States	Research Site	Westminster	Maryland
United States	Research Site	Westwood	Kansas
United States	Research Site	Whittier	California
United States	Research Site	Winston-salem	North Carolina
United States	Research Site	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival	Progression free survival was defined as the time interval from the date of randomization to the date of first disease progression (as assessed by Independent Radiologic Review (IRR) based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria), or the date of death due to any cause, whichever occurred first.; In the absence disease progression or death, the participant was censored at the date of the last valid tumor assessment performed before the cut-off date.	until cut-off date established from deaths rate	No
Primary	Overall survival	Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause.; In the absence of confirmation of death, participant was censored at the last date he/she was known to be alive, or at the cut-off date, whichever was earlier.	until cut-off date established from deaths rate	No
Secondary	Best overall response	Best overall response was defined as the best evaluation observed through the entire treatment period as assessed by Independent Radiologic Review [IRR] based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria.	until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)	No
Secondary	Objective response rate	Objective response rate was defined as the percentage of patients with IRR confirmed partial response or complete response prior to disease progression or treatment discontinuation.	until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)	No