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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03329183
• Other study ID #: HFSFF
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2019
• Est. completion date: March 2022

Study information

• Verified date: February 2019
• Source: Shanghai Changzheng Hospital
• Contact: Yuan-Sheng Zang, Prof
• Phone: +8613816584620
• Email: doctorzangys[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 2022
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Irinotecan
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)

Locations

Country	Name	City	State
China	Shanghai Changzheng Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Changzheng Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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