Combination Chemotherapy in Treating Patients With Unresectable Metastatic Colorectal Cancer

Sponsor

Medical Research Council (Other)

Overall Status

Completed

CT.gov ID

NCT00008060

Collaborator

(none)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for advanced colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil combined with leucovorin and either irinotecan or oxaliplatin in treating patients who have unresectable metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: FOLFIRI regimen Drug: FOLFOX regimen Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: oxaliplatin	Phase 3

Detailed Description

OBJECTIVES:

Compare the efficacy of combination chemotherapy comprising fluorouracil (5-FU) with leucovorin calcium (CF) and either irinotecan (CPT-11) or oxaliplatin vs standard sequential single-agent therapy comprising 5-FU with CF followed by CPT-11 in patients with unresectable metastatic colorectal cancer.
Determine whether combination chemotherapy is best used as first-line therapy or reserved for second-line therapy after progression on first-line single-agent therapy in these patients.
Compare the efficacy and toxicity of an irinotecan-containing regimen vs an oxaliplatin-containing regimen in these patients.
Compare the overall survival, progression-free survival, and quality of life of patients treated with these regimens.
Compare the safety and toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to one of five treatment arms.

Arm I (standard therapy): Patients receive first-line chemotherapy comprising leucovorin calcium IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46 hours on days 1-2 every 14 days. Patients with progressive disease then receive second-line therapy comprising irinotecan IV over 90 minutes on day 1 every 21 days.
Arm II: Patients receive first-line chemotherapy as in arm I. Patients with progressive disease then receive second-line therapy comprising irinotecan IV over 30 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2 every 14 days.
Arm III: Patients receive first-line chemotherapy comprising irinotecan, leucovorin calcium, and fluorouracil as in second-line therapy of arm II.
Arm IV: Patients receive first-line chemotherapy as in arm I. Patients with progressive disease then receive second-line therapy comprising leucovorin calcium IV and oxaliplatin IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46 hours on days 1-2 every 14 days.
Arm V: Patients receive first-line chemotherapy comprising leucovorin calcium, oxaliplatin, and fluorouracil as in second-line therapy of arm IV.

Treatment continues in all arms in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 6 and 12, and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 2,100 patients (700 in arm I and 350 each in arms II-V) will be accrued for this study.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing: A Randomized Trial to Assess the Role of Irinotecan and Oxaliplatin in Advanced Colorectal Cancer

Study Start Date :

May 1, 2000

Actual Study Completion Date :

Dec 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic adenocarcinoma of the colon or rectum
Unresectable disease
Measurable or evaluable disease
No partial or complete bowel obstruction

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

WHO 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC greater than 4,000/mm^3
Platelet count greater than 150,000/mm^3

Hepatic:

Bilirubin less than 1.25 times upper limit of normal (ULN)
Alkaline phosphatase less than 5 times ULN
AST or ALT less than 3 times ULN
No Gilbert's syndrome or other congenital abnormality of biliary transport (e.g., Crigler-Najjar syndrome or Dubin-Johnson syndrome)