LCI-BRE-MTN-NIR-001: A Phase I Study of Niraparib in Combination With Standard Chemotherapy in Metastatic Triple-Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Stage 1 - Evaluate dose-limiting toxicities (DLT) separately for Arms 1, 2, 3, and 4 and establish recommended Stage 2 dose of chemotherapy in combination with niraparib
研究概览
简要总结
This is an open-label, two-stage, multi-arm Phase 1 study designed to evaluate the safety and preliminary efficacy of combining niraparib with four standard chemotherapy regimens used to treat TNBC.
详细描述
Niraparib is an oral, selective poly ADP ribose polymerase (PARP)-1 and PARP-2 inhibitor. A strategy of combining a PARP inhibitor, as a chemopotentiator, with chemotherapy is a promising approach in the treatment of triple-negative breast cancer. This study will evaluate the combination of niraparib with several standard chemotherapy regimens used to treat breast cancer to determine a recommended Stage 2 dose (RS2D) of chemotherapy regimens with niraparib. Stage 1 will be conducted in subjects with metastatic TNBC and will include 4 chemotherapy treatment arms in escalating dose levels (Arm 1: doxorubicin + cyclophosphamide (AC) every 14 days with pegfilgrastim (or biosimilar) for 4 cycles followed by AC every 21 days; Arm 2: AC every 21 days; Arm 3: weekly paclitaxel; Arm 4: weekly paclitaxel + carboplatin every 21 days), each combined with oral daily niraparib. Treatment will continue until disease progression, unacceptable toxicity, or subject withdrawal.Stage 2 will be conducted in subjects with non-metastatic TNBC. Subjects will receive neoadjuvant chemotherapy with either AC every 14 days (Arm 1A) or every 21 days (Arm 2A) at the RS2D of chemotherapy combined with oral daily niraparib from Stage 1. Treatment will continue for 4 cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
Stage 1 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles, followed by AC IV every 21 days
干预措施: Niraparib (Drug)
Stage 1 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles, followed by AC IV every 21 days
干预措施: Doxorubicin (Drug)
Stage 1 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles, followed by AC IV every 21 days
干预措施: Cyclophosphamide (Drug)
Stage 1 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles, followed by AC IV every 21 days
干预措施: Pegfilgrastim (Drug)
Stage 1 Arm 2
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days
干预措施: Niraparib (Drug)
Stage 1 Arm 2
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days
干预措施: Doxorubicin (Drug)
Stage 1 Arm 2
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days
干预措施: Cyclophosphamide (Drug)
Stage 1 Arm 3
Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, 15, and 22 every 28 days
干预措施: Niraparib (Drug)
Stage 1 Arm 3
Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, 15, and 22 every 28 days
干预措施: Paclitaxel (Drug)
Stage 1 Arm 4
Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, and 15 every 21 days and carboplatin IV every 21 days
干预措施: Niraparib (Drug)
Stage 1 Arm 4
Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, and 15 every 21 days and carboplatin IV every 21 days
干预措施: Paclitaxel (Drug)
Stage 1 Arm 4
Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, and 15 every 21 days and carboplatin IV every 21 days
干预措施: Carboplatin (Drug)
Stage 2 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles
干预措施: Niraparib (Drug)
Stage 2 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles
干预措施: Doxorubicin (Drug)
Stage 2 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles
干预措施: Cyclophosphamide (Drug)
Stage 2 Arm 1
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles
干预措施: Pegfilgrastim (Drug)
Stage 2 Arm 2
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days
干预措施: Niraparib (Drug)
Stage 2 Arm 2
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days
干预措施: Doxorubicin (Drug)
Stage 2 Arm 2
Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Stage 1 - Evaluate dose-limiting toxicities (DLT) separately for Arms 1, 2, 3, and 4 and establish recommended Stage 2 dose of chemotherapy in combination with niraparib
时间窗: up to 28 days
The DLT variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined DLT.
Stage 2 - Assess clinically significant toxicities separately for Arms 1 and 2 after RS2D of niraparib is determined.
时间窗: up to 84 days
The clinically significant toxicity variable will be determined for each subject as a binary variable indicating whether or not the subject experienced a niraparib-related dose delay of at least 28 days or a Grade 3 or higher niraparib-related non-hematologic toxicity.
次要结局
- Stage 2 - Overall safety profile - Complete Blood Count with Differential (CBCD)(up to 4 weeks post-surgery)
- Stage 1 - Objective response rate (ORR)(up to 30 days post-treatment discontinuation)
- Stage 1 - Duration of response (DoR)(up to 5 years post-treatment discontinuation)
- Stage 1 - Clinical benefit rate (CBR)(up to 30 days post-treatment discontinuation)
- Stage 1 - Progression free survival (PFS)(up to 5 years post-treatment discontinuation)
- Stage 1 - Overall survival (OS)(up to 5 years post-treatment discontinuation)
- Stage 1 - Cumulative incidence of secondary malignancies including MDS(up to 5 years post-treatment discontinuation)
- Stage 1 - Overall safety profile - Adverse Events of Special Interest (AESIs)(up to 30 days post-treatment discontinuation)
- Stage 1 - Overall safety profile - Adverse Events (AEs)(up to 30 days post-treatment discontinuation)
- Stage 1 - Overall safety profile - Death on Study Therapy(up to 30 days post-treatment discontinuation)
- Stage 1 - Overall safety profile - Complete Blood Count with Differential (CBCD)(up to 30 days post-treatment discontinuation)
- Stage 1 - Overall safety profile - Comprehensive Metabolic Profile (CMP)(up to 30 days post-treatment discontinuation)
- Stage 2 - Cumulative incidence of secondary malignancies including MDS(up to 5 years post-treatment discontinuation)
- Stage 2 - Overall safety profile - Death on Study Therapy(up to 4 weeks post-surgery)
- Stage 2 - Overall safety profile - Comprehensive Metabolic Profile (CMP)(up to 4 weeks post-surgery)
- Stage 2 - Pathologic complete response (pCR)(up to 4 weeks post-surgery)
- Stage 2 - Overall safety profile - Adverse Events of Special Interest (AESIs)(up to 4 weeks post-surgery)
- Stage 2 - Overall safety profile - Adverse Events (AEs)(up to 4 weeks post-surgery)
- Stage 2 - Clinical complete response (cCR)(up to 4 weeks post-surgery)
- Stage 2 - Overall survival(up to 5 years post-treatment discontinuation)
- Stage 2 - Relapse-free survival(up to 5 years post-treatment discontinuation)
- Stage 2 - Overall safety profile - Serious Adverse Events (SAEs)(up to 4 weeks post-surgery)