Combination Chemotherapy in Treating Patients With Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs at the time of day that allows for the best drug response may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Randomized phase II trial to determine the best time to give irinotecan combined with fluorouracil, leucovorin, and oxaliplatin in treating patients who have colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the role of peak delivery time on the tolerability of irinotecan when administered with chronomodulated fluorouracil, leucovorin calcium, and oxaliplatin as first- or second-line therapy in patients with locoregional or metastatic colorectal cancer. Determine the antitumor activity of this regimen. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, WHO performance status (0-1 vs 2), and line of treatment (first vs second). Patients are randomized to receive irinotecan at 1 of 6 different times of the day. Patients receive irinotecan IV over 6 hours on day 1 and fluorouracil IV and leucovorin calcium IV over 11 hours followed by oxaliplatin IV over 11 hours on days 2-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 4 weeks until disease progression and then every 8 weeks thereafter. PROJECTED ACCRUAL: A maximum of 186 patients (31 per irinotecan administration time) will be accrued for this study within 2 years.

Official Title
-----------------
Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer

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

Intervention / Treatment
-----------------
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed colorectal cancer Unresectable metastatic or locoregional disease At least 1 measurable lesion outside a previously irradiated area or an area treated with physical devices (e.g., cryotherapy, laser, or thermoablation) No prior enrollment in EORTC-05963 No symptomatic brain metastases PATIENT CHARACTERISTICS: Age: Over 18 Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: Neutrophil count greater than 2,000/mm^3 Platelet count at least 90,000/mm^3 Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) Renal: Creatinine no greater than 1.5 times ULN No uncontrolled hypercalcemia Cardiovascular: No overt cardiac disease Pulmonary: No severe respiratory illness Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Male patients must use effective barrier contraception during and for up to 6 months after study No baseline diarrhea greater than grade I (must have less than 4 stools per 24 hours) No prior grade III or IV toxicity related to irinotecan No sensory or motor neuropathy with functional impairment No prior hypersensitivity to any study drug No other primary tumor except basal cell skin cancer or carcinoma in situ of the cervix No uncontrolled infectious or chronic disease No psychological, familial, sociological, or geographical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent prophylactic growth factor therapy Chemotherapy: At least 1 month since prior chemotherapy No prior irinotecan, fluorouracil, leucovorin calcium, and oxaliplatin as combination therapy Other prior therapy containing irinotecan and/or oxaliplatin allowed No more than 1 prior chemotherapy regimen for metastatic or locoregional disease Adjuvant chemotherapy considered first-line therapy if tumor relapsed within 6 months of completion of therapy Endocrine therapy: No concurrent corticosteroids except for emergencies Radiotherapy: See Disease Characteristics Palliative radiotherapy for bone lesion allowed except for disease progression Surgery: See Disease Characteristics

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy, excluding those who stopped prior to course 3 for reasons other than toxicity |  |  | 
| Peak delivery time for CPT11 activity over the first 3 courses |  |  | 
| Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses |  |  | 
| Severe toxic events assessed by CTC v2.0 after each course of chemotherapy |  |  | 
| Progression-free survival |  |  | 
| Overall survival |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer