High-dose FOLFIRI in Advanced Colorectal Cancer Patients With Wild-type UGT1A1*6 and *28

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HD-FOLFIRI<br>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.) | Drug: Irinotecan<br>* 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)<br>* Other names: CPT-11;|
| No Intervention: SD-FOLFIRI<br>Advanced CRC patients with Wild-type UGT1A1*6 and *28 receive standard-dose FOLFIRI regimen (Irinotecan 180mg/m2 2h, leucovorin 400mg/m2, 5- fluorouracil 400mg/m2 , 5- fluorouracil 2400 mg/m2 46h, 14 days per course) | |
| No Intervention: SD-FOLFOX-6<br>Advanced CRC patients with Wild-type UGT1A1*6 and *28 receive standard-dose FOLFOX-6 regimen (Oxaliplatin 130mg/m2 2h, leucovorin 400mg/m2, 5- fluorouracil 400mg/m2 , 5- fluorouracil 2400 mg/m2 46h, 14 days per course) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | 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. | up to 55 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early tumor shrinkage (ETS) rate | (ETS) rate is defined as 20% reduction in target lesions after the first 6 weeks of treatment (first tumor assessment) | up to 55 months | 
| Disease Control Rate (DCR) | 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 | up to 55 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irinotecan, UGT1A1, Advanced Colorectal Cancer