Study of SAR240550 (BSI-201) in Combination With Gemcitabine/Carboplatin, in Patients With Metastatic Triple Negative Breast Cancer
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Purpose
Primary Objective:
- To assess the objective response rate (ORR) of SAR240550 administered as a 60min intravenous infusion twice weekly or weekly, in combination with gemcitabine/carboplatin chemotherapy regimen in patients with metastatic Triple Negative Breast Cancer (mTNBC)
Secondary Objectives:
- To assess the clinical benefit rate (CBR) defined as the rate of complete response (CR), partial response (PR) and stable disease (SD) lasting at least 24 weeks
- To assess Progression-free survival (PFS) and the overall survival (OS)
- To assess the safety profile of each schedule of SAR240550
- To evaluate the pharmacokinetic (PK) profile of SAR240550 (optional)
- To characterize molecular and biological profile of tumors (optional)
Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer, Metastatic |
Drug: Iniparib (SAR240550 - BSI-201) Drug: Gemcitabine Drug: Carboplatin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Multicenter, Randomized, Open Label Study Evaluating a Poly(ADP-ribose) Polymerase-1(PARP-1) Inhibitor, SAR240550 (BSI-201), Administered Twice Weekly or Weekly, in Combination With Gemcitabine/Carboplatin, in Patients With Metastatic Triple Negative Breast Cancer (mTNBC) |
- Overall response rate (ORR) as defined in the RECIST 1.1 version, as: complete response (CR) rate and partial response (PR) rate [ Time Frame: up to a maximum follow up of 14 months ] [ Designated as safety issue: No ]
- Clinical benefit rate (CBR) defined in the RECIST 1.1 version, as complete response (CR) rate + partial response (PR) rate+ stable disease (SD)≥24weeks rate [ Time Frame: up to a maximum follow up of 14 months ] [ Designated as safety issue: No ]
- Progression - free survival assessed according to RECIST 1.1 version [ Time Frame: up to a maximum follow up of 20 months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: up to a maximum follow up of 20 months ] [ Designated as safety issue: No ]
| Enrollment: | 163 |
| Study Start Date: | February 2010 |
| Study Completion Date: | November 2012 |
| Primary Completion Date: | May 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: SAR240550 twice weekly schedule
Gemcitabine will be administered at 1000mg/m² as a 30min intravenous (IV) infusion and carboplatin AUC 2 as a 60min IV infusion at Day 1 and Day 8 every 3 weeks (corresponding to 1 cycle). SAR240550 will be administered at the dose of 5.6mg/kg as a 60min IV infusion. Patients will receive SAR240550 infusions twice weekly (days 1, 4, 8 and 11) for a total dose of 22.4mg/kg per cycle. |
Drug: Iniparib (SAR240550 - BSI-201)
Pharmaceutical form: solution for infusion Route of administration: intravenous Pharmaceutical form: solution for infusion Route of administration: intravenous Pharmaceutical form: solution for infusion Route of administration: intravenous |
|
Experimental: SAR240550 weekly schedule
Gemcitabine will be administered at 1000mg/m² as a 30min IV infusion and carboplatin AUC 2 as a 60min IV infusion at Day 1 and Day 8 every 3 weeks (corresponding to 1 cycle). SAR240550 will be administered at the dose of 11.2 mg/kg as a 60min IV infusion. Patients will receive SAR240550 infusions weekly (days 1, 8) for a total dose of 22.4mg/kg per cycle. |
Drug: Iniparib (SAR240550 - BSI-201)
Pharmaceutical form: solution for infusion Route of administration: intravenous Pharmaceutical form: solution for infusion Route of administration: intravenous Pharmaceutical form: solution for infusion Route of administration: intravenous |
Detailed Description:
The duration of the study for a patient includes a period for inclusion of up to 3 weeks. The patients may continue treatment until disease progression, unacceptable toxicity or consent withdrawal, followed by a minimum of 30-day follow-up after the last study treatment administration.
In case of discontinuation of study treatment, the patient will be considered as withdrawn from study treatment, and will be followed as planned for at least 30 days after the last administration of study treatment for safety purpose. In case of study treatment discontinuation without disease progression, efficacy data will be collected every 6 weeks until disease progression, death or end of study whatever comes first. After disease progression, the patient will be followed-up every 12 weeks (3 months) for overall survival until death or end of study.
The patients who benefit from the study treatment can continue until disease progression, toxicity or willingness to stop.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
Histologically documented breast cancer (either primary or metastatic site) that is:
- ER (Estrogen Receptor)- negative, PR (Progesterone Receptor)-negative (for ER- and PR-negative: <10% tumor staining by immunohistochemistry [IHC]) AND
- Human Epidermal Growth Factor 2 (HER2) non-overexpressing by IHC (0,1+) or, IHC 2+ and Fluorescence In Situ Hybridization (FISH negative). Patients IHC 3+ are not eligible;
- Metastatic breast cancer with measurable disease by the revised guideline for Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1 criteria);
Prior treatment that includes:
- never having received anticancer therapy for metastatic disease OR
- having received 1 or 2 prior chemotherapy regimens in the metastatic setting (prior neo-adjuvant/adjuvant systemic therapy is considered as a prior chemotherapy if the first relapse occurred less than one year after the last treatment administration);
Exclusion criteria:
- Prior treatment with gemcitabine, carboplatin, cisplatin or any PARP inhibitor;
- Bone metastasis as only disease location (except for bone metastasis with measurable soft tissue component);
- Major medical conditions that might affect study participation e.g., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and Locations| Australia | |
| Sanofi-Aventis Investigational Site Number 036002 | |
| Parkville, Australia, 3052 | |
| Sanofi-Aventis Investigational Site Number 036001 | |
| Perth, Australia, 6000 | |
| Sanofi-Aventis Investigational Site Number 036003 | |
| Westmead, Australia, 2145 | |
| Belgium | |
| Sanofi-Aventis Investigational Site Number 056001 | |
| Bruxelles, Belgium, 1000 | |
| Sanofi-Aventis Investigational Site Number 056002 | |
| Leuven, Belgium, 3000 | |
| France | |
| Sanofi-Aventis Investigational Site Number 250005 | |
| Besancon Cedex, France, 25030 | |
| Sanofi-Aventis Investigational Site Number 250003 | |
| Bordeaux, France, 33076 | |
| Sanofi-Aventis Investigational Site Number 250002 | |
| Dijon, France, 21034 | |
| Sanofi-Aventis Investigational Site Number 250004 | |
| Paris, France, 75970 | |
| Sanofi-Aventis Investigational Site Number 250006 | |
| Paris Cedex 05, France, 75231 | |
| Sanofi-Aventis Investigational Site Number 250001 | |
| Toulouse, France, 31052 | |
| Italy | |
| Sanofi-Aventis Investigational Site Number 380004 | |
| Genova, Italy, 16132 | |
| Sanofi-Aventis Investigational Site Number 380001 | |
| Milano, Italy, 20133 | |
| Sanofi-Aventis Investigational Site Number 380002 | |
| Modena, Italy, 41100 | |
| Sanofi-Aventis Investigational Site Number 380003 | |
| Udine, Italy, 33100 | |
| Netherlands | |
| Sanofi-Aventis Investigational Site Number 528001 | |
| Rotterdam, Netherlands, 3075 EA | |
| Spain | |
| Sanofi-Aventis Investigational Site Number 724002 | |
| Barcelona, Spain, 08035 | |
| Sanofi-Aventis Investigational Site Number 724004 | |
| Madrid, Spain, 28050 | |
| Sanofi-Aventis Investigational Site Number 724001 | |
| Málaga, Spain, 29010 | |
| Sanofi-Aventis Investigational Site Number 724003 | |
| Valencia, Spain, 46010 | |
| Study Director: | Clinical Sciences & Operations | Sanofi |
More Information
No publications provided
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT01045304 History of Changes |
| Other Study ID Numbers: | TCD11418, 2009-016091-80 |
| Study First Received: | January 7, 2010 |
| Last Updated: | June 17, 2013 |
| Health Authority: | Belgium: Federal Agency for Medicinal Products and Health Products |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Gemcitabine Carboplatin Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on June 18, 2013