A Phase 2, Randomized, Open-label Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-line Treatment of Metastatic Colorectal Cancer in Patients With a KRAS or NRAS Mutation
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 110
- 试验地点
- 55
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to assess 2 different doses of onvansertib to select the lowest dose that is maximally effective, and to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of onvansertib in combination with FOLFIRI + bevacizumab or FOLFOX + bevacizumab in patients with KRAS or NRAS-mutated metastatic colorectal cancer (CRC) in the first-line setting.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic colorectal cancer.
- •Documented KRAS or NRAS mutation.
- •No previous systemic therapy in the metastatic setting.
- •Participants must be willing to submit archival tissue or undergo fresh biopsy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Women of childbearing potential must use contraception or take measures to avoid pregnancy.
- •Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis and other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib.
- •Must have acceptable organ function
排除标准
- •Concomitant KRAS or NRAS and BRAF-V600 mutation or microsatellite instability high/deficient mismatch repair.
- •Prior treatment with a VEGF inhibitor, including bevacizumab or biosimilars.
- •Previous oxaliplatin treatment within 12 months prior to randomization, when arm open.
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- •Anticancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug.
- •Untreated or symptomatic brain metastasis.
- •Gastrointestinal (GI) disorder(s) that would significantly impede the absorption of an oral agent.
- •Unable or unwilling to swallow study drug.
- •Uncontrolled intercurrent illness.
- •Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxalipatin.
- •Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
- •Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers.
- •QTc >470
研究组 & 干预措施
Onvansertib 30 mg + Standard of Care (SOC)
Participants will receive 30 mg of onvansertib + on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: FOLFIRI (Drug)
Onvansertib 20mg + Standard of Care
Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI/BEV on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Onvansertib (Drug)
Onvansertib 30 mg + Standard of Care
Participants will receive 30 mg onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: FOLFOX (Drug)
Onvansertib 30 mg + Standard of Care
Participants will receive 30 mg onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Bevacizumab (Drug)
Onvansertib 30 mg + Standard of Care
Participants will receive 30 mg onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Onvansertib (Drug)
Onvansertib 20mg + Standard of Care
Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI/BEV on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: FOLFIRI (Drug)
Onvansertib 20 mg + Standard of Care
Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: FOLFOX (Drug)
Standard of Care
Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: FOLFOX (Drug)
Standard of Care (SOC)
Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: FOLFIRI (Drug)
Onvansertib 30 mg + Standard of Care (SOC)
Participants will receive 30 mg of onvansertib + on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Onvansertib (Drug)
Onvansertib 20mg + Standard of Care
Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI/BEV on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Bevacizumab (Drug)
Onvansertib 30 mg + Standard of Care (SOC)
Participants will receive 30 mg of onvansertib + on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Bevacizumab (Drug)
Standard of Care (SOC)
Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Bevacizumab (Drug)
Onvansertib 20 mg + Standard of Care
Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Onvansertib (Drug)
Onvansertib 20 mg + Standard of Care
Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Bevacizumab (Drug)
Standard of Care
Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to approximately 1 year
ORR defined as the proportion of participants who achieved a best overall Response (BOR) of CR or PR per RECIST Version 1.1 from randomization until disease progression, or death due to any cause, as determined by blinded independent central review.
次要结局
- Overall Response (OR)(Up to approximately 1 year)
- Overall Survival (OS)(Up to approximately 1 year)
- Maximum Concentration (Cmax) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab(Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days))
- Area Under the Plasma Concentration Curve (AUC) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab(Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days))
- Efficacy: Exposure Response Evaluation of Onvansertib(Up to approximately 1 year)
- Progression Free Survival (PFS)(Up to approximately 1 year)
- Number of Participants with an Adverse Event (AE)(Up to approximately 1 year)
- Duration of Response (DOR)(Up to approximately 1 year)
- Disease Control Rate (DCR)(Up to approximately 1 year)
- Safety: Exposure Response Evaluation of Onvansertib(Up to approximately 1 year)
- Trough Concentration (Ctrough) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab(Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days))