Two Regimens of SAR240550/Weekly Paclitaxel and Paclitaxel Alone as Neoadjuvant Therapy in Triple Negative Breast Cancer Patients
- Conditions
- Breast Cancer Female
- Interventions
- Registration Number
- NCT01204125
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
- to assess the pathological Complete Response (pCR) rate in the breast of patients treated in following combinations: SAR240550 twice-weekly + weekly paclitaxel, SAR240550 weekly+ weekly paclitaxel, and weekly paclitaxel single agent as calibrator.
Secondary objectives are:
* pCR rate in the breast and axilla,
* Radiological/clinical objective response rate (ORR), breast conservation rate, disease free survival (DFS), and overall survival (OS), in each treatment arm,
* Safety profiles of study combinations and of the single agent reference treatment,
* Molecular characteristics of the tumor tissue and peripheral blood mononuclear cells (PBMC) and any correlation between the biological activity of the study treatment and the disease outcome.
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.
- Detailed Description
Active study treatment will be given either as twice weekly administration (Day 1 and Day 4) or as weekly administration (Day 1) for a maximum of 24 infusions for Arm A and for a maximum of 12 infusions for Arm B. In all study arms, treatment will be given until definitive surgery, the first sign of disease progression, unacceptable toxicity or withdrawal of patient consent.
Definitive surgery will be performed within 2 to 4 weeks after the last dose of study treatment.
Patients who complete all the study treatment or who withdraw consent or experience intolerable toxicity will undergo surgery according to local practices.
The cut-off date for the primary analyses will be 30 days after the last study treatment administration or the date of the definitive surgery, whichever comes last.
The maximum follow up for each individual patient will be until death or 5 years after the definitive surgery date whatever happens first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 141
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR240550 weekly/ paclitaxel weekly Iniparib (SAR2405550 -BSI-201) SAR240550 will be administered at the dose of 11.2 mg/kg as a 60-min intravenous (IV) infusion. Patients will receive SAR240550 infusions once weekly (day 1; total dose of 11.2mg/kg per week) and paclitaxel weekly as a 60-min IV infusion (day 1; dose of 80mg/m2). Paclitaxel alone paclitaxel Paclitaxel will be administered at the dose of 80mg/m2 as a 60-min IV infusion. Patients will receive weekly (day 1) paclitaxel infusions. SAR240550 twice weekly/ paclitaxel weekly Iniparib (SAR2405550 -BSI-201) SAR240550 will be administered at the dose of 5.6mg/kg as a 60-min intravenous (IV) infusion. Patients will receive SAR240550 infusions twice weekly (day 1 and day 4; total dose of 11.2mg/kg per week) and paclitaxel weekly as a 60-min IV infusion (day 1; dose of 80mg/m2).
- Primary Outcome Measures
Name Time Method Pathological Complete Response (pCR) rate defined as the complete absence of invasive carcinoma on histological examination of the breast at the time of definitive surgery and confirmed by blinded centralized review at the time of definitive surgery
- Secondary Outcome Measures
Name Time Method Pathological Complete Response (pCR) rate in the breast and axilla at the time of definitive surgery Objective Response Rate(ORR) defined in the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as complete response rate + partial response rate at the time of definitive surgery Breast conservation rate at the time of definitive surgery Disease Free Survival rate (DFS) up to a maximum of 5 years after definitive surgery Overall Survival (OS) up to a maximum of 5 years after definitive surgery Safety parameters (number of patients AE, SAE or AEPM) up to a maximum of 5 years after definitive surgery Molecular-biological testing 2 or 3 timepoints during treatment period
Trial Locations
- Locations (25)
Investigational Site Number 250002
🇫🇷Toulouse, France
Investigational Site Number 250001
🇫🇷Besancon Cedex, France
Investigational Site Number 250004
🇫🇷Bordeaux, France
Investigational Site Number 276002
🇩🇪Köln, Germany
Investigational Site Number 276004
🇩🇪Hamburg, Germany
Investigational Site Number 724016
🇪🇸Madrid, Spain
Investigational Site Number 724012
🇪🇸Jaén, Spain
Investigational Site Number 724006
🇪🇸Islas Baleares, Spain
Investigational Site Number 724002
🇪🇸Lérida, Spain
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 724005
🇪🇸Madrid, Spain
Investigational Site Number 276003
🇩🇪Erlangen, Germany
Investigational Site Number 250006
🇫🇷Bron Cedex, France
Investigational Site Number 250003
🇫🇷Paris Cedex 10, France
Investigational Site Number 276001
🇩🇪Mönchengladbach, Germany
Investigational Site Number 724009
🇪🇸Cáceres, Spain
Investigational Site Number 724013
🇪🇸Córdoba, Spain
Investigational Site Number 724018
🇪🇸Santiago De Compostela, Spain
Investigational Site Number 724017
🇪🇸Sevilla, Spain
Investigational Site Number 724007
🇪🇸Reus, Spain
Investigational Site Number 724010
🇪🇸Sevilla, Spain
Investigational Site Number 724003
🇪🇸Torrevieja, Spain
Investigational Site Number 724015
🇪🇸Valencia, Spain
Investigational Site Number 250005
🇫🇷Villejuif, France
Investigational Site Number 724011
🇪🇸Valencia, Spain