A Phase 1/1b Dose Escalation Study Evaluating Iniparib (BSI201/SAR240550) as a Single Agent and in Combination With Chemotherapeutic Regimens in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 59
- 试验地点
- 6
- 主要终点
- Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle
研究概览
简要总结
Primary Objective:
- To assess the safety and the maximum tolerated dose(MTD) of iniparib as a single agent and in combination with chemotherapeutic regimens in patients with advanced solid tumors that are refractory to standard therapy.
Secondary Objectives:
- To assess the antitumor effect of iniparib (per Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease.
- To characterize iniparib (and its metabolites, if possible) pharmacokinetics.
Based on data generated by 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
The duration of the study for an individual patient will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (3 weeks or 4 weeks depending on regimen) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue until precluded by toxicity, progression, or death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 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
Iniparib, single agent
Iniparib will be initially administered intravenously once weekly (days 1, 8, and 15) for 3 weeks, in a 21-day cycle. Then, iniparib will be administered twice weekly (days 1, 4, 8, 11, 15, and 18) in a 21-day cycle. Cycle1 (day 1 thru day 21) will be defined as the dose limiting toxicities (DLT) observation period. Starting dose is 15 mg/kg once weekly.
干预措施: Iniparib (SAR240550-BSI-201) (Drug)
Iniparib/Gemcitibine/Carboplatin
Gemcitabine/carboplatin (GC) : Gemcitabine will be administered at 1,000 mg/m² as a 30min IV infusion and carboplatin area under the curve (AUC) 2 as a 60min IV infusion. Patients will receive gemcitabine/carboplatin infusions once weekly (days 1 and 8). Iniparib will be administered for two weeks, followed by a 1week of rest in a 21-day cycle (weekly schedule: days 1 and 8; twice weekly schedule: days: 1, 4, 8 and 11).
干预措施: Iniparib (SAR240550-BSI-201) (Drug)
Iniparib/Gemcitibine/Carboplatin
Gemcitabine/carboplatin (GC) : Gemcitabine will be administered at 1,000 mg/m² as a 30min IV infusion and carboplatin area under the curve (AUC) 2 as a 60min IV infusion. Patients will receive gemcitabine/carboplatin infusions once weekly (days 1 and 8). Iniparib will be administered for two weeks, followed by a 1week of rest in a 21-day cycle (weekly schedule: days 1 and 8; twice weekly schedule: days: 1, 4, 8 and 11).
干预措施: Gemcitabine (Drug)
Iniparib/Gemcitibine/Carboplatin
Gemcitabine/carboplatin (GC) : Gemcitabine will be administered at 1,000 mg/m² as a 30min IV infusion and carboplatin area under the curve (AUC) 2 as a 60min IV infusion. Patients will receive gemcitabine/carboplatin infusions once weekly (days 1 and 8). Iniparib will be administered for two weeks, followed by a 1week of rest in a 21-day cycle (weekly schedule: days 1 and 8; twice weekly schedule: days: 1, 4, 8 and 11).
干预措施: Carboplatin (Drug)
Iniparib/Paclitaxel
Paclitaxel (P): Paclitaxel will be administered at the dose of 80 mg/m2 as a 60-minute intravenous infusion administered on days 1, 8, and 15 followed by a 1week of rest. Iniparib will be administered for three weeks, followed by 1week of rest in a 28-day cycle (weekly schedule: days 1, 8 and 15; twice weekly schedule: days 1, 4, 8, 11, 15 and 18).
干预措施: Iniparib (SAR240550-BSI-201) (Drug)
Iniparib/Paclitaxel
Paclitaxel (P): Paclitaxel will be administered at the dose of 80 mg/m2 as a 60-minute intravenous infusion administered on days 1, 8, and 15 followed by a 1week of rest. Iniparib will be administered for three weeks, followed by 1week of rest in a 28-day cycle (weekly schedule: days 1, 8 and 15; twice weekly schedule: days 1, 4, 8, 11, 15 and 18).
干预措施: Placlitaxel (Drug)
Iniparib/Pegylated liposomal doxorubicin/Carboplatin
Pegylated liposomal doxorubicin (Doxil)/Carboplatin (PLD) : Doxil will be administered at 30 mg/m² as a 30min IV infusion and carboplatin AUC 4 as a 60min IV infusion on day 1 every four weeks. Iniparib will be administered for two weeks in a 28-day cycle (weekly schedule: days 1, and 8; twice weekly schedule: days 1, 4, 8, and 11).
干预措施: Iniparib (SAR240550-BSI-201) (Drug)
Iniparib/Pegylated liposomal doxorubicin/Carboplatin
Pegylated liposomal doxorubicin (Doxil)/Carboplatin (PLD) : Doxil will be administered at 30 mg/m² as a 30min IV infusion and carboplatin AUC 4 as a 60min IV infusion on day 1 every four weeks. Iniparib will be administered for two weeks in a 28-day cycle (weekly schedule: days 1, and 8; twice weekly schedule: days 1, 4, 8, and 11).
干预措施: Carboplatin (Drug)
Iniparib/Pegylated liposomal doxorubicin/Carboplatin
Pegylated liposomal doxorubicin (Doxil)/Carboplatin (PLD) : Doxil will be administered at 30 mg/m² as a 30min IV infusion and carboplatin AUC 4 as a 60min IV infusion on day 1 every four weeks. Iniparib will be administered for two weeks in a 28-day cycle (weekly schedule: days 1, and 8; twice weekly schedule: days 1, 4, 8, and 11).
干预措施: Pegylated liposomal doxorubicin (Drug)
结局指标
主要结局
Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle
时间窗: 3 - 4 weeks
次要结局
- To assess the antitumor effect of iniparib according to the Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease(Up to 2 years)
- Pharmakokinetic (PK) parameters : tmax(0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose)
- Pharmakokinetic (PK) parameters: Cmax(0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose)
- Pharmakokinetic (PK) parameters: tlast(0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose)
- Pharmakokinetic (PK) parameters: AUC(0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose)
- Pharmakokinetic (PK) parameters : t1/2z(0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose)