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
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
3 other identifiers
interventional
519
1 country
102
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 breast-cancer
Started Jul 2009
Shorter than P25 for phase_3 breast-cancer
102 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2009
CompletedFirst Submitted
Initial submission to the registry
July 10, 2009
CompletedFirst Posted
Study publicly available on registry
July 14, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2012
CompletedSeptember 19, 2013
September 1, 2013
1.5 years
July 10, 2009
September 13, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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
Secondary Outcomes (2)
Best overall response
until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
Objective response rate
until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
Study Arms (2)
Arm G/C
ACTIVE COMPARATORgemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)
Arm G/C/I
EXPERIMENTALgemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s)
Interventions
Gemcitabine 1000 mg/m2 intravenous infusion (30 ± 10 minutes) Carboplatin AUC 2 intravenous infusion (30 ± 10 minutes or 60 ± 10 minutes)
Body weight adjusted dose intravenous infusion (60 ± 10 minutes)
Eligibility Criteria
You may qualify if:
- \- 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;
- +1 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sanofilead
Study Sites (102)
Research Site
Birmingham, Alabama, United States
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Sedona, Arizona, United States
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Jonesboro, Arkansas, United States
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Alhambra, California, United States
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Bakersfield, California, United States
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Campbell, California, United States
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Fullerton, California, United States
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Lancaster, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Nothridge, California, United States
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Oxnard, California, United States
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Palo Alto, California, United States
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Pomona, California, United States
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Redondo Beach, California, United States
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San Francisco, California, United States
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Santa Barbara, California, United States
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Santa Maria, California, United States
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Sylmar, California, United States
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Vallejo, California, United States
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Westlake Village, California, United States
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Whittier, California, United States
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Denver, Colorado, United States
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Grand Junction, Colorado, United States
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Washington D.C., District of Columbia, United States
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Bonita Springs, Florida, United States
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Gainesville, Florida, United States
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Hollywood, Florida, United States
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Jacksonville, Florida, United States
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Miami, Florida, United States
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Ocala, Florida, United States
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Ocoee, Florida, United States
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Orange Park, Florida, United States
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Orlando, Florida, United States
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Port Saint Lucie, Florida, United States
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Albany, Georgia, United States
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Athens, Georgia, United States
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Atlanta, Georgia, United States
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Augusta, Georgia, United States
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Lawrenceville, Georgia, United States
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Macon, Georgia, United States
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Marietta, Georgia, United States
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Savannah, Georgia, United States
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Coeur d'Alene, Idaho, United States
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Chicago, Illinois, United States
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Indianapolis, Indiana, United States
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Overland Park, Kansas, United States
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Westwood, Kansas, United States
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Baltimore, Maryland, United States
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Chevy Chase, Maryland, United States
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Westminster, Maryland, United States
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Boston, Massachusetts, United States
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Ann Arbor, Michigan, United States
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Royal, Michigan, United States
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Minneapolis, Minnesota, United States
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Rochester, Minnesota, United States
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Jackson, Mississippi, United States
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Columbia, Missouri, United States
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St Louis, Missouri, United States
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Billings, Montana, United States
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Grand Island, Nebraska, United States
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Las Vegas, Nevada, United States
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Hooksett, New Hampshire, United States
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Morristown, New Jersey, United States
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Sparta, New Jersey, United States
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Santa Fe, New Mexico, United States
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Amsterdam, New York, United States
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East Setauket, New York, United States
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New York, New York, United States
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Chapel Hill, North Carolina, United States
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Charlotte, North Carolina, United States
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Durham, North Carolina, United States
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Durham, North Carolina, United States
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Greensboro, North Carolina, United States
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Raleigh, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Cincinnati, Ohio, United States
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Toledo, Ohio, United States
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Portland, Oregon, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Columbia, South Carolina, United States
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Chattanooga, Tennessee, United States
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Memphis, Tennessee, United States
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Nashville, Tennessee, United States
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Austin, Texas, United States
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Bedford, Texas, United States
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Dallas, Texas, United States
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Fort Worth, Texas, United States
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Fredericksburg, Texas, United States
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Houston, Texas, United States
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Tyler, Texas, United States
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Salt Lake City, Utah, United States
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Fairfax, Virginia, United States
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Norfolk, Virginia, United States
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Richmond, Virginia, United States
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Roanoke, Virginia, United States
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Suffolk, Virginia, United States
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Kennewick, Washington, United States
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Seattle, Washington, United States
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Vancouver, Washington, United States
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Yakima, Washington, United States
Related Publications (1)
O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014 Dec 1;32(34):3840-7. doi: 10.1200/JCO.2014.55.2984. Epub 2014 Oct 27.
PMID: 25349301DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Sciences & Operations
Sanofi
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
July 10, 2009
First Posted
July 14, 2009
Study Start
July 1, 2009
Primary Completion
January 1, 2011
Study Completion
February 1, 2012
Last Updated
September 19, 2013
Record last verified: 2013-09