Randomized Phase 2 Study of Valproic Acid Combined With Rechallenge Anti-EGFR Based Regimen Regimens in Pretreated Patients With RAS/BRAF Wild-type Metastatic Colorectal Cancer - VICTORIA Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 130
- 试验地点
- 8
- 主要终点
- Study Part 1 - Progression Free Survival rate at 16 weeks in the two arms.
研究概览
简要总结
The investigators hypothesize that the epigenetic agent valproic acid improve the activity of anti-EGFR agents, prevent and revert the emergence of EGFR resistance, in a rechallenge setting.
Correlative mechanistic studies on tissue and blood samples, liquid biopsies, could identify potential biomarkers of efficacy and help understanding the evolutionary dynamics of tumors in response to therapy thus optimizing the treatment approach with a personalized anti- EGFR treatment strategy.
详细描述
This study is a multicentric open label academic randomized phase-2 study. The study population will include patients with advanced or metastatic colorectal cancer, RAS/BRAF wt mCRC, eligible for a rechallenge setting (third or later line), with RAS/BRAF wt ctDNA status at study entry. A total of 130 patients (65/arm) will be required.
The VICTORIA - Study Part 1 is a phase 2, open label, randozimed study. Before starting study Part 1 treatment, at the time of enrollment, patients will be randomized electronically 1:1 to one of the two arms: ARM A (standard treatment: irinotecan + panitimumab) and ARM B (VPA + irinotecan + panitumumab) Each cycle will be administered every two weeks for both arms. Patients will continue to receive study treatment until treatment failure as previous defined, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
All subjects who finish treatment, whichever the reason, will enter in the follow-up. All patients will be followed until death and data on subsequent treatment will be collected.
VPA will be administered per os daily with a titration strategy (table 2 of the protocol) to improve the compliance for the treatment, with a target serum level between 50 and 100 μg/mL that represents the recommended values for epilepsy and also a useful concentration to produce the desired synergistic effect with chemotherapy based on preclinical studies (0.5- 1mM).
An initial safety run-in phase involves a safety evaluation after the first 6 patients are randomly assigned to Arm B. Enrollment will be paused after the first 6 patients randomly assigned to Arm B complete 2 cycles of treatment. The enrollment will be interrupted if the treatment combination will be judged not feasible and major safety concerns will arise. A safety review will be conducted, and recommendations will be made by the Steering Committee. The study will continue if there are 2 or fewer adverse events (AEs) of grade 3 or higher deemed related to the addition of valproic acid to the panitumumab + irinotecan.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
STUDY PART 1 - ARM B - experimental arm
Patients will continue to receive standard rechallenge with irinotecan and panitumumab in combination with VPA until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
干预措施: panitumumab (Drug)
STUDY PART 1 - ARM A - control arm
Patients will continue to receive standard rechallenge with irinotecan and panitumumab until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
干预措施: irinotecan (Drug)
STUDY PART 1 - ARM A - control arm
Patients will continue to receive standard rechallenge with irinotecan and panitumumab until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
干预措施: panitumumab (Drug)
STUDY PART 1 - ARM B - experimental arm
Patients will continue to receive standard rechallenge with irinotecan and panitumumab in combination with VPA until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
干预措施: irinotecan (Drug)
STUDY PART 1 - ARM B - experimental arm
Patients will continue to receive standard rechallenge with irinotecan and panitumumab in combination with VPA until treatment failure, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria.
干预措施: Valproic Acid (VPA) (Drug)
结局指标
主要结局
Study Part 1 - Progression Free Survival rate at 16 weeks in the two arms.
时间窗: up to 16 weeks from randomization
Progression Free Survival rate at 16 weeks (PFS rate at 16-weeks) is defined as the rate of assessable patients alive and not progressed after 16 weeks from initiation of VICTORIA - Study Part 1 (i.e randomization) to the first documentation of objective disease progression by RECIST 1.1 criteria, or death due to any cause, whichever occurs first.
次要结局
- Study Part 1: Progression free survival (PFS)(up to 1 year last patients randomized)
- Study Part 1 - Overall survival (OS)(up to 1 year last patients randomized)
- Study Part 1: Objective Tumor Response Rate (ORR)(up to 1 year last patients randomized)
- Study Part 1: Disease Control Rate (DCR)(up to 1 year last patients randomized)
- Study Part 1: Overall Toxicity rate(up to 1 year last patients randomized)
- Study Part 1 - Quality of life (QoL)(up the date of first documented progression (assessed up to 1 year))