Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy such as irinotecan, capecitabine, leucovorin, and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of colorectal cancer by stopping blood flow to the tumor. It is not yet known which combination chemotherapy regimen with or without celecoxib is more effective in treating metastatic colorectal cancer. PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens and celecoxib to see how well they work compared to two combination chemotherapy regimens alone in treating patients with metastatic colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Compare the progression-free survival of patients with metastatic colorectal cancer treated with capecitabine and irinotecan vs fluorouracil, leucovorin calcium, and irinotecan with vs without celecoxib. Compare the safety of these regimens in these patients. Compare the response rate in patients treated with these regimens. Compare the time to treatment failure and overall survival of patients treated with these regimens. OUTLINE: This is a randomized, double-blind*, multicenter study. Patients are stratified according to participating center, prior adjuvant therapy (yes vs no), and risk group (poor vs intermediate vs good). Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive irinotecan IV over 30-90 minutes on days 1 and 22; oral capecitabine twice daily on days 1-15 and 22-36; and oral celecoxib twice daily on days 1-42. Arm II: Patients receive irinotecan and capecitabine as in arm I and oral placebo twice daily on days 1-42. Arm III: Patients receive irinotecan IV over 30-90 minutes on days 1, 15, and 29; leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1, 2, 15, 16, 29, and 30; and oral celecoxib twice daily on days 1-42. Arm IV: Patients receive irinotecan, CF, and 5-FU as in arm III and oral placebo twice daily on days 1-42. In all arms, treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. If all chemotherapy is discontinued due to toxicity, patients may continue celecoxib or placebo until disease progression, unacceptable toxicity, or starting a new cytotoxic regimen. NOTE: *The double-blind treatment only applies to the celecoxib and placebo randomization Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 692 patients (173 per treatment arm) will be accrued for this study within 3.5 years.

Official Title
-----------------
Irinotecan Combined With Infusional 5-FU/Folinic Acid or Capecitabine and the Role of Celecoxib in Patients With Metastatic Colorectal Cancer

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: FOLFIRI regimen
* Drug: capecitabine
* Drug: celecoxib
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum Metastatic disease Measurable disease Patients who received prior radiotherapy must have measurable or evaluable disease outside the radiotherapy field No CNS metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 2 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN (5 times ULN in the presence of liver metastases) Renal Creatinine clearance at least 51 mL/min No severe renal impairment Cardiovascular No severe cardiac disease No uncontrolled angina pectoris No myocardial infarction within the past 6 months Other Not pregnant or nursing Fertile patients must use effective contraception during and for 6 months after study participation No active Crohn's disease No other malignancy except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer No other uncontrolled severe medical condition No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent active or passive immunotherapy for colon cancer Chemotherapy No prior chemotherapy for metastatic disease Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery Not specified Other At least 6 months since prior adjuvant therapy More than 4 weeks since prior investigational drugs No concurrent sorivudine or chemically related analogues (e.g., brivudine) No other concurrent investigational drugs No other concurrent cytotoxic agents No concurrent prophylactic fluconazole No concurrent or planned cyclo-oxygenase-2 (COX-2) inhibitors or nonsteroidal anti-inflammatory drugs No concurrent chronic use of full-dose aspirin (325 mg/day or greater) Concurrent low-dose (cardioprotective) aspirin prophylaxis (no more than 325 mg every other day OR no more than 162.5 mg per day) allowed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFIRI regimen|nan|
|Drug: capecitabine|nan|
|Drug: celecoxib|nan|
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: leucovorin calcium|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the colon, adenocarcinoma of the rectum, stage IV colon cancer, stage IV rectal cancer