Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer - A Proof of Concept, Open Label Non-randomized Phase IIa Study. The AVETUXIRI Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 59
- 试验地点
- 2
- 主要终点
- Tumor response rate
研究概览
简要总结
Cancer immunotherapy with immunostimulatory antibodies targeting the CTLA-4 or PD-1/PD-L1 pathways has demonstrated its efficacy in variable proportions of cancer. For metastatic colorectal cancer (mCRC) it appeared that only the small subgroup of patients with MSI-H tumors (microsatellite instability-high phenotype) had a clinically meaningful response to the anti-PD-1- L1 antibodies. In the majority group of non-MSI-H CRC (90-95% of patients), current research expect that additional means would be able to render the tumor "immunogenic" (like MSI-H CRC) and increase the intratumoral immune infiltrate which is the prerequisite to observe a benefit from PD1-PD-L1 inhibitors. Combinations of immune checkpoint inhibitors and procedures that increase intratumoral immune responses, such as targeted therapy, are actively explored.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 and over, Performance status: ECOG 0-1
- •Histologically proven metastatic colorectal adenocarcinoma, refractory to standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan) and anti-EGFR treatment (only for RAS WT tumor)
- •Measurable disease (RECIST 1.1)
- •Metastasis accessible for sequential biopsies
- •Patient consent for metastasis biopsies in the study protocol
- •BRAF V600E wild-type and MSS tumors
- •Adequate normal organ and marrow function (see adequate section of the full protocol for definition)
- •Life expectancy of at least 4 months
排除标准
- •Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy that are not indicated in the study protocol
- •Systemic autoimmune disease,
- •Chronic treatment with corticoids or other immunosuppressive treatment
- •Clinically significant cardiac, lung or general disease despite optimal treatment
- •Non-progressive disease following irinotecan-based treatment.
- •For RAS WT, non-progressive disease following anti-EGFR treatment.
研究组 & 干预措施
Avelumab, Cetuximab, Irinotecan
Avelumab : administrated at a fixed dose of 10 mg/kg once every 2- week. Cetuximab: administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3.
Irinotecan: administrated every 2 weeks (180 mg/m2).
干预措施: Avelumab (Drug)
Avelumab, Cetuximab, Irinotecan
Avelumab : administrated at a fixed dose of 10 mg/kg once every 2- week. Cetuximab: administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3.
Irinotecan: administrated every 2 weeks (180 mg/m2).
干预措施: Cetuximab Injection (Drug)
Avelumab, Cetuximab, Irinotecan
Avelumab : administrated at a fixed dose of 10 mg/kg once every 2- week. Cetuximab: administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3.
Irinotecan: administrated every 2 weeks (180 mg/m2).
干预措施: Irinotecan (Drug)
结局指标
主要结局
Tumor response rate
时间窗: Up to 19 weeks
The overall tumor response rate (ORR) defined as the proportion of all included patient with a confirmed best overall tumor response of PR or CR according to irRECIST 1.1 occuring until 19 weeks after study treatment start.
次要结局
- Adverse events(Up to 19 weeks)