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

Primary Purpose

Colorectal Cancer

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Irinotecan
Sponsored by
Shanghai Changzheng Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Irinotecan, UGT1A1, Advanced Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Shanghai Changzheng HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

No Intervention

Arm Label

HD-FOLFIRI

SD-FOLFIRI

SD-FOLFOX-6

Arm Description

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.)

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)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)
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

Full Information

First Posted
October 25, 2017
Last Updated
February 14, 2019
Sponsor
Shanghai Changzheng Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03329183
Brief Title
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

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 2019 (Anticipated)
Primary Completion Date
March 2019 (Anticipated)
Study Completion Date
March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Changzheng Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Irinotecan, UGT1A1, Advanced Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HD-FOLFIRI
Arm Type
Experimental
Arm Description
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.)
Arm Title
SD-FOLFIRI
Arm Type
No Intervention
Arm Description
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)
Arm Title
SD-FOLFOX-6
Arm Type
No Intervention
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
CPT-11
Intervention Description
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 Measure Information:
Title
Objective Response Rate(ORR)
Description
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.
Time Frame
up to 55 months
Secondary Outcome Measure Information:
Title
Early tumor shrinkage (ETS) rate
Description
(ETS) rate is defined as 20% reduction in target lesions after the first 6 weeks of treatment (first tumor assessment)
Time Frame
up to 55 months
Title
Disease Control Rate (DCR)
Description
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
Time Frame
up to 55 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuan-Sheng Zang, Prof
Phone
+8613816584620
Email
doctorzangys@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuan-Sheng Zang, Prof
Organizational Affiliation
Shanghai Changzheng Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200433
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuan-sheng Zang, Prof.
Phone
+8613816584620
Email
doctorzangys@163.com

12. IPD Sharing Statement

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

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