High-dose FOLFIRI in Advanced Colorectal Cancer Patients With Wild-type UGT1A1*6 and *28
- Registration Number
- NCT03329183
- Lead Sponsor
- Shanghai Changzheng Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 90
- 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
- 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;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HD-FOLFIRI Irinotecan 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.)
- Primary Outcome Measures
Name Time Method Objective Response Rate(ORR) 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.
- Secondary Outcome Measures
Name Time Method Early tumor shrinkage (ETS) rate up to 55 months (ETS) rate is defined as 20% reduction in target lesions after the first 6 weeks of treatment (first tumor assessment)
Disease Control Rate (DCR) up to 55 months Evaluation of tumor burden based on RECIST criteria every 4 cycles(each cycle is 14 days), and DCR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response, partial response and stable disease
Trial Locations
- Locations (1)
Shanghai Changzheng Hospital
🇨🇳Shanghai, Shanghai, China