A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib With Bevacizumab Plus Folfox or Folfiri as First Line Therapy in Patients With PIK3CA-Mutated Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 164
- 主要终点
- Safety Run-in Period: Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
This is a blinded Phase 2 study designed to evaluate the safety and efficacy of inavolisib with bevacizumab and chemotherapy, in participants with metastatic colorectal cancer (mCRC) whose tumors have a PIK3CA mutation. The study has a safety run-in period followed by a randomized period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Eastern Cooperative Oncology Group (ECOG) <=1
- •Histologically confirmed adenocarcinoma originating in the colon or rectum of the Stage 4 ( treatment plan does not include resection or curative ablation) per American Joint Committee on Cancer (AJCC) v8
- •Measurable disease per RECIST v1.1
- •No prior systemic therapy in the metastatic setting
- •Confirmation of biomarker eligibility: documentation of a PIK3CA mutation from either central testing of tissue, or from a validated historically obtained (pre-existing) test of tumor tissue or blood may be used to confirm eligibility
- •Adequate hematologic and organ function within 14 days prior to initiation of study treatment
- •Agreement to adhere to the contraception requirements
排除标准
- •Biomarker eligibility as per definition
- •Type 2 diabetes requiring ongoing systemic treatment at the time of study entry or any history of Type 1 diabetes
- •Residual Grade 2 or higher neuropathy due to prior oxaliplatin exposure (unless the participant is planned to be treated with FOLFIRI)
- •Symptomatic, untreated, or actively progressing CNS metastases
- •History of gastrointestinal (GI) fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 1 of Cycle 1
- •Treatment with strong cytochrome P450 (CYP) 3A4 inducers or strong CYP3A4 inhibitors within 1 week or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment (only for patients who will receive FOLFIRI)
- •Known HIV positive status with exceptions for well controlled and on stable treatment
- •History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
研究组 & 干预措施
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Inavolisib.
干预措施: Inavolisib (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Inavolisib.
干预措施: Bevacizumab (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Inavolisib.
干预措施: FOLFOX (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Inavolisib.
干预措施: FOLFIRI (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Placebo.
干预措施: Bevacizumab (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Placebo.
干预措施: FOLFOX (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Placebo.
干预措施: FOLFIRI (Drug)
Randomized Period: FOLFOX or FOLFIRI + Bevacizumab + Placebo
Participants will receive either FOLFOX or FOLFIRI and Bevacizumab along with Placebo.
干预措施: Placebo (Drug)
Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFIRI or FOLFOX and Bevacizumab along with Inavolisib.
干预措施: Inavolisib (Drug)
Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFIRI or FOLFOX and Bevacizumab along with Inavolisib.
干预措施: Bevacizumab (Drug)
Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFIRI or FOLFOX and Bevacizumab along with Inavolisib.
干预措施: FOLFOX (Drug)
Safety Run-in Period: FOLFOX or FOLFIRI + Bevacizumab + Inavolisib
Participants will receive either FOLFIRI or FOLFOX and Bevacizumab along with Inavolisib.
干预措施: FOLFIRI (Drug)
结局指标
主要结局
Safety Run-in Period: Percentage of Participants With Adverse Events (AEs)
时间窗: Approximately 4 Years
Percentage of Participants With an Objective Response Rate
时间窗: From Baseline Untill Radiographic Disease Progression (Approximately 4 Years)
The percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1.)
次要结局
- Progression-free Survival (PFS)(From Baseline Untill Radiographic Disease Progression (up to Approximately 4 Years))
- Randomized Phase: Overall Survival (OS)(From Baseline Untill Death (up to Approximately 4 Years))
- Randomized Phase: Disease Control Rate (DCR)(From Baseline Untill Disease Progression (up to Approximately 4 Years))
- Randomized Phase: Duration of Response (DOR)(From Baseline Untill Disease Progression or Death (up to Approximately 4 Years))
- Randomized Phase: Percentage of Participants With AEs(From Baseline up to 90 Days After the Final Dose of study treatment or Until Initiation of Another Anti-cancer Therapy (up to Approximately 4 Years))
- Percentage of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)(Up to Approximately 4 Years)
- Percentage of Participants Troubled by Treatment Symptoms, as Assessed by Single Item European Organisation for Research and Treatment of Cancer Item Library 46 (EORTC IL46)(Up to Approximately 4 Years)
- Change From Baseline in Symptomatic Treatment Toxicities as Assessed by PRO-CTCAE(Baseline up to Approximately 4 Years)
- Change From Baseline in Treatment Side-effect Bother as Assessed by EORTC IL46 item(Baseline up to Approximately 4 Years)