Breast CancerPhase 3NCT00938652
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 study testing gemcitabine/carboplatin and Iniparib in people with Breast Cancer, run by Sanofi at 102 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- gemcitabine/carboplatin and Iniparib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 519 participants
- Where
- 102 sitesUnited States
- Study dates
- Jul 2009to Feb 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
Trial locations and contacts
102 sites in 1 country.
102 sites in 1 country
United States102 sites
Research Site
Albany, Georgia
Research Site
Alhambra, California
Research Site
Amsterdam, New York
Research Site
Ann Arbor, Michigan
Research Site
Athens, Georgia
Research Site
Atlanta, Georgia
Research Site
Augusta, Georgia
Research Site
Austin, Texas
Research Site
Bakersfield, California
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Baltimore, Maryland
Research Site
Bedford, Texas
Reserach Site
Billings, Montana
Research Site
Birmingham, Alabama
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Bonita Springs, Florida
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Boston, Massachusetts
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Campbell, California
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Chapel Hill, North Carolina
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Charlotte, North Carolina
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Chattanooga, Tennessee
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Chevy Chase, Maryland
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Chicago, Illinois
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Cincinnati, Ohio
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Coeur d'Alene, Idaho
Research Site
Columbia, Missouri
Reserach Site
Columbia, South Carolina
Research Site
Dallas, Texas
Research Site
Denver, Colorado
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Durham, North Carolina
Reserach Site
Durham, North Carolina
Research Site
East Setauket, New York
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Fairfax, Virginia
Research Site
Fort Worth, Texas
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Fredericksburg, Texas
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Fullerton, California
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Gainesville, Florida
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Grand Island, Nebraska
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Grand Junction, Colorado
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Greensboro, North Carolina
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Hollywood, Florida
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Hooksett, New Hampshire
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Houston, Texas
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Indianapolis, Indiana
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Jackson, Mississippi
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Jacksonville, Florida
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Jonesboro, Arkansas
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Kennewick, Washington
Research Site
Lancaster, California
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Las Vegas, Nevada
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Lawrenceville, Georgia
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Long Beach, California
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Los Angeles, California
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Macon, Georgia
Research Site
Marietta, Georgia
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Memphis, Tennessee
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Miami, Florida
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Minneapolis, Minnesota
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Morristown, New Jersey
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Nashville, Tennessee
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New York, New York
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Norfolk, Virginia
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Nothridge, California
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Ocala, Florida
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Ocoee, Florida
Research Site
Orange Park, Florida
Research Site
Orlando, Florida
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Overland Park, Kansas
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Oxnard, California
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Palo Alto, California
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Philadelphia, Pennsylvania
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Pittsburgh, Pennsylvania
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Pomona, California
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Port Saint Lucie, Florida
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Portland, Oregon
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Raleigh, North Carolina
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Redondo Beach, California
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Richmond, Virginia
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Roanoke, Virginia
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Rochester, Minnesota
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Royal, Michigan
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Salt Lake City, Utah
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San Francisco, California
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Santa Barbara, California
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Santa Fe, New Mexico
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Santa Maria, California
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Savannah, Georgia
Research Sites
Seattle, Washington
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Sedona, Arizona
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Sparta, New Jersey
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St Louis, Missouri
Research Site
Suffolk, Virginia
Research Site
Sylmar, California
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Toledo, Ohio
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Tyler, Texas
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Vallejo, California
Research Site
Vancouver, Washington
Research Site
Washington D.C., District of Columbia
Research Site
Westlake Village, California
Research Site
Westminster, Maryland
Research Site
Westwood, Kansas
Research Site
Whittier, California
Research Site
Winston-Salem, North Carolina
Research Site
Yakima, Washington
About this study
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
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.
Read the detailed 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.
- Conditions
- Breast Cancer
- Being tested
- gemcitabine/carboplatin, Iniparib
- Keywords
- triple negative breast cancer, metastatic breast cancer, Triple negative metastatic breast cancer
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gemcitabine/carboplatinDrug
Gemcitabine 1000 mg/m2 intravenous infusion (30 ± 10 minutes)
Carboplatin AUC 2 intravenous infusion (30 ± 10 minutes or 60 ± 10 minutes)
IniparibDrug
Also called BSI-201, SAR240550
Body weight adjusted dose
intravenous infusion (60 ± 10 minutes)
| Study group | Role | What they receive |
|---|---|---|
| Arm G/C | Active comparator | gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s) Receives: Drug: gemcitabine/carboplatin |
| Arm G/C/I | Experimental | gemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s) Receives: Drug: gemcitabine/carboplatin; Drug: Iniparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: until cut-off date established from deaths rate
Secondary outcomes (2)
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.
Measured: until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
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.
Measured: until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionJan 2011
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 519 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00938652
- Sponsor's protocol ID
- EFC11486
- Other IDs
- 20090301, U1111-1119-8208
- Status last verified
- Sep 2013
- First submitted
- 10 Jul 2009
- Last updated
- 19 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
- Expanded access
- Available
Publications
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.
PubMed 25349301
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00938652
- Acronym / sponsor ID
- EFC11486
- Conditions
- Breast Cancer
- Keywords
- triple negative breast cancer, metastatic breast cancer, Triple negative metastatic breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 519 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 14 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm G/C | Active comparator | Drug: gemcitabine/carboplatingemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s) |
| Arm G/C/I | Experimental | Drug: gemcitabine/carboplatin, Drug: Iniparibgemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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).
- 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).
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gemcitabine/carboplatinGemcitabine 1000 mg/m2 intravenous infusion (30 ± 10 minutes) Carboplatin AUC 2 intravenous infusion (30 ± 10 minutes or 60 ± 10 minutes) | Drug | Arm G/C, Arm G/C/I |
| IniparibAlso: BSI-201, SAR240550Body weight adjusted dose intravenous infusion (60 ± 10 minutes) | Drug | Arm G/C/I |
Primary outcome
progression free survival
Time frame: until cut-off date established from deaths rate
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.
Overall survival
Time frame: until cut-off date established from deaths rate
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.
2 secondary outcomes
Best overall response
Time frame: until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
Objective response rate
Time frame: until treatment discontinuation (assessment at the end of cycle 2 then every other cycle)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2013.
- Derived from this study: PubMed 25349301O'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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
102 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing gemcitabine/carboplatin and Iniparib in people with Breast Cancer, run by Sanofi at 102 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 102 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (time frame: until cut-off date established from deaths rate). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00938652, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2013.