Clinical trial NCT03329183: High-dose FOLFIRI in Advanced Colorectal Cancer Patients With Wild-type UGT1A1*6 and *28
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Irinotecan
UGT1A1
Advanced Colorectal Cancer
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2017-11-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Objective Response Rate(ORR)
timeFrame: up to 55 months
Secondary outcomes:
measure: Early tumor shrinkage (ETS) rate
timeFrame: up to 55 months
measure: Disease Control Rate (DCR)
timeFrame: up to 55 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Changzheng Hospital
name: Yuan-Sheng Zang, Prof
role: PRINCIPAL_INVESTIGATOR
References: