Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00004931

Collaborator

(none)

2,472

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

Randomized phase III trial to compare the effectiveness of fluorouracil plus leucovorin with or without oxaliplatin in treating patients who have stage II or stage III colon cancer. 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 combination chemotherapy regimen is more effective for colon cancer

Condition or Disease	Intervention/Treatment	Phase
Stage II Colon Cancer Stage III Colon Cancer	Drug: leucovorin calcium Drug: fluorouracil Drug: oxaliplatin Other: laboratory biomarker analysis	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

To compare the relative efficacy of 5-FU + LV + Oxaliplatin (FLOX) with that of 5-FU + LV (FL) in prolonging DFS.

SECONDARY OBJECTIVES:

To compare the relative efficacy of FLOX with FL in prolonging S.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

ARM I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.

ARM II: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.

Treatment in both arms repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 6, 9, and 12 months; every 6 months for 4 years; and then annually thereafter.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2472 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Clinical Trial Comparing 5-Fluorouracil (5-FU) Plus Leucovorin (LV) and Oxaliplatin With 5-FU Plus LV for the Treatment of Patients With Stages II and III Carcinoma of the Colon

Study Start Date :

Feb 1, 2000

Actual Primary Completion Date :

Sep 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.	Drug: leucovorin calcium Given IV Other Names: CF CFR LV Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU Other: laboratory biomarker analysis Correlative studies
Experimental: Arm II Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.	Drug: leucovorin calcium Given IV Other Names: CF CFR LV Drug: fluorouracil Given IV Other Names: 5-fluorouracil 5-Fluracil 5-FU Drug: oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.

Drug: leucovorin calcium

Given IV

Other Names:

CFR

Drug: fluorouracil

Given IV

Other Names:

5-fluorouracil

5-Fluracil

5-FU

Other: laboratory biomarker analysis

Correlative studies

Experimental: Arm II

Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.

Drug: leucovorin calcium

Given IV

Other Names:

CFR

Drug: fluorouracil

Given IV

Other Names:

5-fluorouracil

5-Fluracil

5-FU

Drug: oxaliplatin

Given IV

Other Names:

1-OHP

Dacotin

Dacplat

Eloxatin

L-OHP

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

DFS rate [Time to first documented evidence of colon cancer recurrence, second primary cancer, or death from any cause without prior evidence of colon cancer recurrence or second primary cancer, assessed up to 3 years]

Secondary Outcome Measures

Survival rate [Time to death from any cause, assessed up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines
In the opinion of the investigator, patients must have a 10-year life expectancy, excluding their diagnosis of cancer
The interval between curative resection and randomization must be no more than 42 days
The distal extent of the tumor must be >= 12 cm from the anal verge on endoscopy
Patients must have colonic adenocarcinoma that meets one of the criteria below:
Stage II carcinoma (T3, 4; N0; M0) - The tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues (T3) or directly invades other organs or structures, and/or perforates visceral peritoneum (T4), excluding free perforation
Stage III carcinoma (any T; N1, 2; M0) - The tumor has invaded to any depth, with involvement of regional lymph nodes
AGCs >= 1500/mm^3
Platelets >= 100,000/mm^3
Bilirubin within or below the normal limits for the laboratory
Alkaline phosphatase within or below the normal limits for the laboratory
SGOT or SGPT within or below the normal limits for the laboratory
Serum creatinine within or below the normal limits for the laboratory
Patients with more than one synchronous primary colon tumor are eligible; for the purpose of this protocol, staging classification will be based on the stage of the more advanced primary tumor
Patients are eligible if adjacent structures (e.g., bladder, small intestine, ovary, etc.) involved by direct extension of the primary tumor are removed en bloc and if, in the judgement of the surgeon and by confirmation on histological examination (i.e., margins of resection are not involved), the resection is deemed to be "curative"
Patients must have an ECOG performance status of 0, 1, or 2
Patients with intestinal obstruction are eligible; preliminary or complementary colostomy does not preclude entry
Patients with prior noncolorectal malignancies are eligible if they have been disease-free for >= 5 years; patients with squamous or basal cell carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by operation only, or lobular carcinoma in situ of the breast are eligible, even if these conditions were diagnosed within 5 years prior to randomization

Exclusion Criteria:

Prior invasive colon or rectal malignancy, regardless of disease-free interval
Current or past malignant colon tumors other than carcinoma, i.e., sarcoma, lymphoma, carcinoid, etc., regardless of disease-free interval
Tumors located < 12 cm from the anal verge on preoperative endoscopy
Tumors that demonstrate free perforation as manifested by free air or free fluid in the abdomen; patients with walled-off perforation are eligible
Pregnancy or lactation at the time of proposed randomization; (5-FU and oxaliplatin are both teratogenic and mutagenic and may cause fetal harm;) eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods
Noncurative surgical resection or prior chemotherapy or radiotherapy for this malignancy, with the exception of a decompressing colostomy
Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient's receiving either chemotherapy treatment option; specifically excluded are patients with active ischemic heart disease (class III or class IV myocardial disease -- New York Heart Association) or a recent history of myocardial infarction (within 6 months), or current symptomatic arrhythmia
Class III: Patients with cardiac disease resulting in marked limitation of physical activity; such patients are comfortable at rest; less-than-ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain
Class IV: Patients with cardiac disease resulting in inability to perform any physical activity without discomfort; symptoms of cardiac insufficiency or the anginal syndrome may be present even at rest
Psychiatric or addictive disorders that would preclude obtaining informed consent
Multiple primary tumors involving both the colon and the rectum that would preclude the patient's being classified as having only colon cancer
Evidence of laparoscopically-assisted colectomy, unless patients are participating in the Intergroup Protocol INT 0146 or the Australasian, Multi-center, Prospective, Randomized, Clinical Study Comparing Laparoscopic and Conventional Open Surgical Treatments of Colon Cancer in Adults (ALCCaS)
Isolated, distant, or noncontiguous intra-abdominal metastases, even if resected, will render the patient ineligible
Clinically significant peripheral neuropathy at the time of randomization (defined in the NCI Common Toxicity Criteria [CTC] as grade 2 or greater neurosensory or neuromotor toxicity)