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
Overview
- Phase
- Phase 3
- Intervention
- leucovorin calcium
- Conditions
- Stage II Colon Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 2472
- Locations
- 1
- Primary Endpoint
- DFS rate
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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
Detailed Description
PRIMARY OBJECTIVES: I. To compare the relative efficacy of 5-FU + LV + Oxaliplatin (FLOX) with that of 5-FU + LV (FL) in prolonging DFS. SECONDARY OBJECTIVES: I. 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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Arm I
Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.
Intervention: leucovorin calcium
Arm I
Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.
Intervention: fluorouracil
Arm I
Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.
Intervention: laboratory biomarker analysis
Arm II
Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.
Intervention: leucovorin calcium
Arm II
Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.
Intervention: fluorouracil
Arm II
Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.
Intervention: oxaliplatin
Arm II
Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
DFS rate
Time Frame: 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 Outcomes
- Survival rate(Time to death from any cause, assessed up to 5 years)