Study of SAR240550 (BSI-201) in Combination With Gemcitabine/Carboplatin, in Patients With Metastatic Triple Negative Breast Cancer

Study Overview
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Brief Summary
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Primary Objective: To assess the objective response rate (ORR) of iniparib (SAR240550) administered as a 60min intravenous (IV) 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 iniparib; To assess the biological activity in tumor tissue (substudy); To evaluate the pharmacokinetic (PK) profile of iniparib (substudy); To characterize molecular and biological profile of tumors (substudy); To assess the effect of iniparib on poly(ADP)-ribose (PAR) level in peripheral blood mononuclear cells (PBMC) (substudy).

Detailed Description
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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 In case of discontinuation of study treatment, the patient will be considered as withdrawn from study treatment, and will be followed as planned for at least 30 days after the last administration of study treatment for safety purpose.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.

Official Title
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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)

Conditions
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Breast Cancer, Metastatic

Intervention / Treatment
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* Drug: Iniparib
* Drug: Gemcitabine
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically documented breast cancer (either primary or metastatic site) that is ER (estrogen receptor)-negative, PgR (progesterone receptor)-negative ( <10% tumor staining by immunohistochemistry [IHC]) and HER2 (human epidermal growth factor 2) non-overexpressing by IHC (0,1+) or, IHC 2+ and FISH (fluorescence In situ hybridization) negative. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gencitabine + iniparib twice weekly<br>Gemcitabine, 1000 mg/m² IV over 30 minutes and carboplatin, area under the curve (AUC) = 2, IV over 60 minutes, both on Days 1 and 8 of 3-week cycles. Iniparib, 5.6 mg/kg IV over 60 minutes on Days 1, 4, 8 and 11 of 3-week cycles | Drug: Iniparib<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>* Other names: BSI-201;Drug: Gemcitabine<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>Drug: Carboplatin<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>|
| Experimental: Gencitabine + iniparib weekly<br>Gemcitabine, 1000 mg/m² IV over 30 minutes and carboplatin, area under the curve (AUC) = 2, IV over 60 minutes, both on Days 1 and 8 of 3-week cycles. Iniparib, 11.2 mg/kg IV over 60 minutes on Days 1 and 8 of 3-week cycles | Drug: Iniparib<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>* Other names: BSI-201;Drug: Gemcitabine<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>Drug: Carboplatin<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Proportion of participants with confirmed complete response (CR) or partial response (PR) as confirmed by an Independent Radiology Review Committee (IRRC) based on central review of scans in a blinded manner. | Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (CBR) | Proportion of participants with confirmed complete response (CR) or partial response (PR) ot stable disease (SD) greater than 24 weeks as confirmed by the IRRC. | Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months) | 
| Progression-free survival | Number of days from the date of randomization to the date of disease progression (ie, radiological progression based on IRRC assessment) or the date of death (from any cause), whichever is earlier. | Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months) | 
| Overall survival |  | Up the cut-off date for analysis defined as 16 weeks after the 1st dose in the last participant (maximum follow-up of 14 months) |