Irinotecan or Fluorouracil Plus Leucovorin in Treating Patients With Previously Treated Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more tumor cells. PURPOSE: Phase II trial to compare the effectiveness of either irinotecan or fluorouracil plus leucovorin in treating patients who have metastatic colorectal cancer that has been previously treated with oxaliplatin with or without irinotecan.

Detailed Description
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OBJECTIVES: Determine the tumor response rate in patients receiving irinotecan or fluorouracil and leucovorin calcium for metastatic colorectal cancer previously treated with oxaliplatin with or without irinotecan. Determine the time to tumor progression, time to treatment failure, and overall survival of patients treated with these regimens. Determine the toxic effects of these regimens in these patients. Evaluate the quality of life of patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (oxaliplatin-based therapy vs irinotecan and oxaliplatin combination therapy). Patients are assigned to one of two treatment groups. Group I (prior oxaliplatin-based chemotherapy): Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks. Group II (prior irinotecan and oxaliplatin combination chemotherapy): Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously on days 1 and 2. Treatment repeats every 2 weeks. Both groups: Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion. Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment. Patients are followed every 3 months for 5 years.

Official Title
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Phase II Study in Patients With Metastatic Colorectal Carcinoma Previously Treated With Oxaliplatin (OXAL) or a Combination of Irinotecan (CPT-11) and OXAL

Conditions
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Colorectal Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of metastatic colorectal adenocarcinoma incurable by surgery or not amenable to radiotherapy with curative intent Progressive disease after one of the following prior treatments for metastatic disease: Oxaliplatin-based chemotherapy Irinotecan and oxaliplatin combination chemotherapy At least 1 measurable lesion At least 20 mm in at least one dimension No known CNS metastases or carcinomatous meningitis PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 0.5 mg/dL above upper limit of normal (ULN) AST no greater than 5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No unstable angina No symptomatic congestive heart failure No serious uncontrolled cardiac arrhythmia Other: No active or uncontrolled infection No evidence of other serious illness No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent sargramostim (GM-CSF) Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy No more than 1 prior chemotherapy regimen for advanced colorectal cancer Prior adjuvant chemotherapy allowed Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to more than 25% of bone marrow Surgery: See Disease Characteristics At least 4 weeks since prior major surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: irinotecan<br>Prior oxaliplatin-based chemotherapy: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion. Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment. Patients are followed every 3 months for 5 years. | Drug: irinotecan hydrochloride<br> <br> |
| Experimental: leucovorin + fluorouracil<br>Prior to irinotecan and oxaliplatin combination chemotherapy: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously on days 1 and 2. Treatment repeats every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion. Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment. Patients are followed every 3 months for 5 years. | Drug: fluorouracil<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor response rate |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to tumor progression |  | Up to 5 years | 
| time to treatment failure |  | Up to 5 years | 
| overall survival |  | Up to 5 years | 
| quality of life |  | Up to 5 years | 

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