Combination Chemotherapy in Treating Patients With Resected Colon Cancer

Sponsor

NSABP Foundation Inc (Other)

Overall Status

Completed

CT.gov ID

NCT00378716

Collaborator

National Cancer Institute (NCI) (NIH)

1,608

Enrollment

Arms

145.9

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 is a way to kill more tumor cells.

PURPOSE: Randomized phase III trial to determine the effectiveness of uracil, tegafur,and leucovorin compared with fluorouracil plus leucovorin in patients with resected stage II or stage III colon cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: 5-fluorouracil Drug: leucovorin calcium Drug: tegafur Drug: uracil	Phase 3

Detailed Description

OBJECTIVES: I. Compare the relative efficacy of oral uracil/tegafur (UFT) with leucovorin (CF) vs. fluorouracil (5-FU) with CF in prolonging overall and disease-free survival in patients with potentially curatively resected stage II/III adenocarcinoma of the colon. II. Compare the prognostic significance of several biomarkers alone or in combination, including DNA mismatch repair gene mutations, p53, deleted colon cancer gene, proliferation status, and thymidylate synthase, in patients treated with UFT/CF vs. 5-FU/CF. III. Evaluate the relationships of various biomarkers to each other and their association with patient and tumor characteristics. IV. Compare quality of life in patients treated with UFT/CF vs. 5-FU/CF.

OUTLINE: This is a randomized study. Patients are stratified by number of positive lymph nodes and participating institution. For the quality-of-life portion of the study, patients are stratified by age, sex, and ethnicity. Treatment begins within 6 weeks after curative resection and within 1 week of randomization. Patients are randomly assigned to one of two groups. The first group receives intravenous leucovorin followed by intravenous fluorouracil weekly for 6 weeks. Treatment repeats every 8 weeks for a total of 3 courses. The second group receives oral uracil/tegafur, and oral leucovorin every 8 hours for 28 days. Treatment repeats every 5 weeks for a total of 5 courses. No concurrent halogenated antiviral agents (e.g., sorivudine) are permitted. After completing treatment, patients complete quality-of-life questionnaires at one year.

PROJECTED ACCRUAL: Approximately 1,500 patients will be entered over 3 years to provide 1,452 evaluable patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

1608 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Clinical Trial Comparing Oral Uracil/Ftorafur (UFT) Plus Leucovorin (LV) With 5-Fluorouracil (5-FU) Plus LV in the Treatment of Patients With Stages II And III Carcinoma of the Colon

Study Start Date :

Feb 1, 1997

Actual Primary Completion Date :

May 1, 2006

Actual Study Completion Date :

Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 5-FU + Leucovorin	Drug: 5-fluorouracil Drug: leucovorin calcium
Experimental: Group 2 Uracil/Ftorarur + leucovorin	Drug: tegafur Drug: uracil

Arm

Intervention/Treatment

Active Comparator: Group 1

5-FU + Leucovorin

Drug: 5-fluorouracil

Drug: leucovorin calcium

Experimental: Group 2

Uracil/Ftorarur + leucovorin

Drug: tegafur

Drug: uracil

Outcome Measures

Primary Outcome Measures

Compare the relative efficacy of UFT + LV with that of 5-FU + LV in prolonging disease-free survival and survival []

Secondary Outcome Measures

evaluate the prognostic significants of proposed biomarkers, alone or in combination, in patients treated with 5-FU + LV or UFT + LV []
Evaluate the relationships of various biomarkers to each other and to evaluate their association with patient and tumor characteristics []
Compare quality of life in patients with stage II and III carcinoma of the colon treated with either 5-FU + LV or UFT + LV regimen []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon that has been curatively resected within 42 days prior to entry, as follows: Stage II (T3-4 N0 M0, Modified Astler-Coller B2/3), i.e., tumor invasion of the wall of the colon or extension into the pericolonic tissue Stage III (any T N1-3 M0), i.e., tumor invasion of any depth No sarcoma, lymphoma, or carcinoid histology No laparoscopically assisted colectomy unless performed on protocol NCCTG-934653 (intergroup study INT-0146) Entire tumor located above the peritoneal reflection on surgical exploration or more than 15 cm from anal verge on endoscopy Involved adjacent structures (e.g., bladder, small intestine, ovary) removed en bloc with histologically negative margins More than 1 synchronous primary colon tumor allowed Most advanced tumor used for stage assignment No previous or synchronous rectal cancer Intestinal obstruction allowed Preliminary or complementary colostomy allowed Walled-off perforation allowed No free perforation, i.e., free air or fluid in abdomen No prior invasive colon or rectal malignancy regardless of disease-free interval

PATIENT CHARACTERISTICS: Age: Not specified Performance status: ECOG 0-2 Life expectancy:

At least 10 years (excluding cancer diagnosis) Hematopoietic: WBC at least 4,000/mm3

Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal AST or ALT normal Renal:

Creatinine normal Cardiovascular: No active ischemic heart disease No NYHA class III/IV status No myocardial infarction within 6 months No symptomatic arrhythmia within 6 months Other: No nonmalignant systemic disease that precludes protocol treatment No psychiatric or addictive disorder that precludes informed consent No second malignancy within 10 years except: Effectively treated nonmelanomatous skin cancer Surgically cured carcinoma in situ of the cervix Lobular carcinoma in situ of the breast No pregnant women Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy