Irinotecan With or Without Oxaliplatin in Treating Patients With Metastatic 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. It is not yet known if irinotecan is more effective with or without oxaliplatin in treating metastatic colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with or without oxaliplatin in treating patients who have metastatic colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Compare the overall survival of patients with metastatic colorectal cancer treated with irinotecan with or without oxaliplatin. Compare the response rate, time to tumor-related worsening of symptoms, time to disease progression, onset and duration of responses, and duration of disease stabilization in these patients treated with these regimens. Compare the safety of these regimens in these patients. OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to Karnofsky performance status (50-60% vs 70-100%), number of metastatic organs involved (1 vs 2 or more), lactic dehydrogenase (no greater than 1.5 times upper limit of normal (ULN) vs greater than 1.5 times ULN), and prior fluorouracil chemotherapy (adjuvant vs first-line treatment for metastatic disease). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive irinotecan IV over 90 minutes on day 1. Arm II: Patients receive oxaliplatin IV over 120 minutes followed by irinotecan IV over 30 minutes on day 1. Courses repeat in each arm every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed at 30 days, every 4 weeks for 3 months, and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 596 patients (298 per arm) will be accrued for this study within 18 months.

Official Title
-----------------
A Multicenter, Open-Label, Randomized, Two-Arm Study of Irinotecan (CPT-11) Versus the Combination of Oxaliplatin + Irinotecan (CPT-11) as Second-Line Treatment of Metastatic Colorectal Carcinoma

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

Intervention / Treatment
-----------------
* Drug: irinotecan hydrochloride
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the colon or rectum Metastatic or recurrent disease that is not amenable to potentially curative treatment Progressive or recurrent disease during or after 1, and only 1, regimen of fluorouracil with or without leucovorin calcium or during or within 6 months after adjuvant chemotherapy with fluorouracil and leucovorin calcium PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT/SGPT no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present) Alkaline phosphatase no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No unstable angina No New York Heart Association class III or IV congestive heart failure No serious cardiac arrhythmia No history of cardiac toxicity from fluorouracil/leucovorin calcium No myocardial infarction within past 6 months Pulmonary: No interstitial pneumonia or extensive and symptomatic fibrosis of the lung Other: No uncontrolled predisposing colonic or small bowel disorder No prior chronic enteropathy, chronic diarrhea, or unresolved bowel obstruction/subobstruction No diabetes No active infection No known current peripheral neuropathy No concurrent active cancer except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix No intolerance of appropriate antiemetics No history of anaphylaxis or potential intolerance to atropine sulfate or loperamide Not pregnant or nursing Negative pregnancy test PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy No prior irinotecan or oxaliplatin No other prior chemotherapy agents except fluorouracil with or without leucovorin calcium as first-line therapy for metastatic disease or in the adjuvant setting Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy to non-target lesions allowed No prior radiotherapy to target lesions unless disease progression is documented within the radiation port At least 3 weeks since prior radiotherapy Surgery: At least 4 weeks since prior major surgical procedure and recovered Prior surgery for primary tumor or metastasis allowed Other: At least 30 days since prior investigational drug No concurrent investigational agents

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: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: irinotecan hydrochloride|nan|
|Drug: oxaliplatin|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
-----------------
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer