Irinotecan With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

Sanofi

Status and phase: Completed; Phase 3

Conditions: Colorectal Cancer

Treatments: Drug: oxaliplatin; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT00012389

SANOFI-EFC4585

CDR0000068524

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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