Randomized, Open-label, Phase 2 Study of the Efficacy and Safety of Weekly Paclitaxel Single-agent and Two Different Regimens of the PARP-1 Inhibitor SAR240550 (BSI-201) in Combination With Weekly Paclitaxel, as Neoadjuvant Therapy in Patients With Stage II-IIIA Triple Negative Breast Cancer (TNBC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 141
- 试验地点
- 25
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR240550 twice weekly/ paclitaxel weekly
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).
干预措施: Iniparib (SAR2405550 -BSI-201) (Drug)
SAR240550 weekly/ paclitaxel weekly
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).
干预措施: Iniparib (SAR2405550 -BSI-201) (Drug)
Paclitaxel alone
Paclitaxel will be administered at the dose of 80mg/m2 as a 60-min IV infusion. Patients will receive weekly (day 1) paclitaxel infusions.
干预措施: paclitaxel (Drug)
结局指标
主要结局
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
时间窗: at the time of definitive surgery
次要结局
- 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)