- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00938652
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Expanded Access
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States
- Research Site
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Arizona
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Sedona, Arizona, United States
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Arkansas
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Jonesboro, Arkansas, United States
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California
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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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Colorado
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Denver, Colorado, United States
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Grand Junction, Colorado, United States
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District of Columbia
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Washington, District of Columbia, United States
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Florida
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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 St Lucie, Florida, United States
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Georgia
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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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Idaho
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Coeur D'alene, Idaho, United States
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Illinois
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Chicago, Illinois, United States
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Indiana
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Indianapolis, Indiana, United States
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Kansas
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Overland Park, Kansas, United States
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Westwood, Kansas, United States
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Maryland
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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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Massachusetts
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Boston, Massachusetts, United States
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Michigan
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Ann Arbor, Michigan, United States
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Royal, Michigan, United States
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Minnesota
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Minneapolis, Minnesota, United States
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Rochester, Minnesota, United States
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Mississippi
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Jackson, Mississippi, United States
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Missouri
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Columbia, Missouri, United States
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St Louis, Missouri, United States
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Montana
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Billings, Montana, United States
- Reserach Site
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Nebraska
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Grand Island, Nebraska, United States
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Nevada
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Las Vegas, Nevada, United States
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New Hampshire
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Hooksett, New Hampshire, United States
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New Jersey
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Morristown, New Jersey, United States
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Sparta, New Jersey, United States
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New Mexico
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Santa Fe, New Mexico, United States
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New York
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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 City, New York, United States
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North Carolina
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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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Ohio
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Cincinnati, Ohio, United States
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Toledo, Ohio, United States
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Oregon
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Portland, Oregon, United States
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Pennsylvania
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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South Carolina
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Columbia, South Carolina, United States
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Tennessee
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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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Texas
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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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Utah
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Salt Lake City, Utah, United States
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Virginia
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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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Washington
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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
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Arm G/C
gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)
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Gemcitabine 1000 mg/m2 intravenous infusion (30 ± 10 minutes) Carboplatin AUC 2 intravenous infusion (30 ± 10 minutes or 60 ± 10 minutes) |
Experimental: Arm G/C/I
gemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s)
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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)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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progression free survival
Time Frame: until cut-off date established from deaths rate
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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
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Overall survival
Time Frame: until cut-off date established from deaths rate
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Best overall response
Time Frame: until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
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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.
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until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
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Objective response rate
Time Frame: until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
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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.
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until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Poly(ADP-ribose) Polymerase Inhibitors
- Gemcitabine
- Carboplatin
- Iniparib
Other Study ID Numbers
- EFC11486
- 20090301 (Other Identifier: BiPar)
- U1111-1119-8208 (Other Identifier: WHO)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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