Fluorouracil and Leucovorin Plus Either Irinotecan or Oxaliplatin With or Without Cetuximab in Treating Patients With Previously Untreated Metastatic Adenocarcinoma of the Colon or Rectum
Summary
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, irinotecan, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one drug with a monoclonal antibody may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective with or without cetuximab in treating metastatic adenocarcinoma (cancer) of the colon or rectum.
PURPOSE: Randomized phase III trial to compare the effectiveness of combining fluorouracil and leucovorin with either irinotecan or oxaliplatin with or without cetuximab in treating patients who have metastatic cancer of the colon or rectum.
Description
OBJECTIVES:
Primary
- Compare the survival rate of patients with previously untreated metastatic adenocarcinoma of the colon or rectum treated with fluorouracil and leucovorin calcium with oxaliplatin or irinotecan and with or without cetuximab.
Secondary
- Determine the level of epidermal growth factor receptor (EGFR) expression in patients treated with these regimens.
- Determine whether expression of EGFR activity, markers of EGFR activity, and serum levels of insulin-like growth factor-1, C-peptide, and insulin-like growth factor binding protein 3 are independent predictors of response rate, time to tumor progression, and survival of patients treated with these regimens.
- Correlate specific germline polymorphisms related to chemotherapy metabolism and resistance with treatment-related toxicity, tumor response, time to tumor progression, and survival of patients treated with these regimens.
- Correlate expression of putative prognostic markers in the tumor with tumor response, time to tumor progression, and survival of patients treated with these regimens.
- Correlate diet, obesity, physical activity, and other lifestyle habits with treatment-related toxicity, progression-free survival, and overall survival of patients treated with these regimens.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior adjuvant therapy (yes vs no) and prior pelvic radiotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.
- Arm I (FOLFIRI): Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on days 1, 15, 29, and 43 and fluorouracil IV continuously over 46-48 hours beginning on days 1, 15, 29, and 43.
- Arm II (FOLFIRI and cetuximab): Patients receive FOLFIRI as in arm I and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.
- Arm III (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on days 1, 15, 29, and 43 and fluorouracil IV continuously over 46-48 hours beginning on days 1, 15, 29, and 43.
- Arm IV (FOLFOX and cetuximab): Patients receive FOLFOX as in arm III and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.
In all arms, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed every 2 months for 2 years and then every 3 months for 3 years.
PROJECTED ACCRUAL: Approximately 2,200 patients (550 per treatment arm) will be accrued for this study within 4.6 years.
Study Design
Allocation: Randomized, Control: Active Control, Masking: Open Label, Primary Purpose: Treatment
Conditions
Colorectal Cancer
Intervention
cetuximab, FOLFIRI regimen, FOLFOX regimen, fluorouracil, irinotecan hydrochloride, leucovorin calcium, oxaliplatin
Location
Northeast Alabama Regional Medical Center
Anniston
Alabama
United States
36207
Status
Active, not recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00077233
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Patient Compliance
Voluntary cooperation of the patient in following a prescribed regimen.
Clinical Protocols
Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy.
Exercise Therapy
A regimen or plan of physical activities designed and prescribed for specific therapeutic goals. Its purpose is to restore normal musculoskeletal function or to reduce pain caused by diseases or injuries.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Milieu Therapy
A treatment program based on manipulation of the patient's environment by the medical staff. The patient does not participate in planning the treatment regimen.
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