High-dose FOLFIRI Versus Standard-dose FOLFIRI or FOLFOX-6 in Advanced Colorectal Cancer Patients With Wild-type UGT1A1*6 and *28: A Randomized, Opened, Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Objective Response Rate(ORR)
研究概览
简要总结
This trial aims to evaluate the efficacy, safety of high-dose FOLFIRI regimen in advanced colorectal cancer patients with wild-type UGT1A1*6 and *28.
详细描述
Pharmacogenetic testing of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 is recommended in clinical practice prior to the administration of irinotecan (CPT-11)-based regimens, such as FOLFIRI regimen in patients with advanced colorectal cancer. To avoid severe toxicity of irinotecan, such as severe neutropenia and diarrhea, patients with UGT1A1 *6/*28 mutation often start with a reduced dose of irinotecan. However, it remains unclear whether high-dose CPT-based regimen (FOLFIRI) could increase clinical efficacy in CRC patients when compared with standard-dose FOLFIRI or FOLFOX-6 regimens. This trial aims to compare the efficacy, safety of high-dose FOLFIRI and standard-dose FOLFIRI or FOLFOX-6 in advanced colorectal cancer patients with UGT1A1*6 G/G and *28 TA6/6.
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
- Single (Investigator)
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
- •Patients should be histologically diagnosed with advanced colorectal adenocarcinoma or postoperative recurrence
- •Patients should be with UGT1A1*28 wild-type TA6/6 and UGT1A1*6 wild-type G/G
- •Patients have measurable lesions
- •Patients are not available for targeted therapy or patients refuse to receive targeted therapy
- •Age should be more than 18 years
- •Performance status should be 0-2
- •Hemoglobin should be more than 9.0 g/dL; Absolute Neutrophil Count should be more than 1,500/mm3; Platelet should be more than 80,000/mm3；Total Bilirubin should be less than 1.5 times of the upper limit of normal value; Alanine aminotransferase and Glutamic-oxaloacetic transaminase should less than 2.5 times of the upper limit of normal value (it can be 5 times if liver metastasis); Creatinine should be be less than 1.5 times of the upper limit of normal value
排除标准
- •Patients with UGT1A1*28 wild-type TA6/7, TA7/7 and UGT1A1*6 wild-type G/A,A/A;
- •Patients with brain metastases;
- •Patients could not tolerate chemotherapy;
- •Patients have secondary primary tumor;
研究组 & 干预措施
HD-FOLFIRI
Advanced CRC patients with Wild-type UGT1A1*6 and *28 receive high-dose FOLFIRI regimen (Irinotecan 260mg/m2 2h, leucovorin 400mg/m2, 5- fluorouracil 400mg/m2 , 5- fluorouracil 2400 mg/m2 46h, 14 days per course.)
干预措施: Irinotecan (Drug)
结局指标
主要结局
Objective Response Rate(ORR)
时间窗: up to 55 months
Evaluation of tumor burden based on RECIST criteria every 4 cycles(each cycle is 14 days), ORR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response and partial response.
次要结局
- Early tumor shrinkage (ETS) rate(up to 55 months)
- Disease Control Rate (DCR)(up to 55 months)
研究者
Zhan Wang
Associate Professor/Associate chief physician
Shanghai Changzheng Hospital