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

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)

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).

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In case of discontinuation of study treatment, the patient will be considered as withdrawn from study treatment, and will be followed as planned for at least 30 days after the last administration of study treatment for safety purpose.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

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.