Combination Chemotherapy in Treating Patients With Resected Colon Cancer

January 8, 2010 updated by: NSABP Foundation Inc

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1608

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Michael J. O'Connell, MD, Allegheny Cancer Center at Allegheny General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 1997

Primary Completion (Actual)

May 1, 2006

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

September 20, 2006

First Submitted That Met QC Criteria

September 20, 2006

First Posted (Estimate)

September 21, 2006

Study Record Updates

Last Update Posted (Estimate)

January 11, 2010

Last Update Submitted That Met QC Criteria

January 8, 2010

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSABP C-06
  • U10CA012027 (U.S. NIH Grant/Contract)
  • NSABP-C-06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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