Colorectal Cancer
Conditions
Keywords
Irinotecan, UGT1A1, Advanced Colorectal Cancer
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.
Interventions
DRUGIrinotecan
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)
Sponsors
Shanghai Changzheng Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Contacts
Primary ContactYuan-Sheng Zang, Prof
Outcome results
None listed