Combination Chemotherapy in Treating Patients With Resected Colon Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:
NCT00378716
First received: September 20, 2006
Last updated: January 8, 2010
Last verified: January 2010
  Purpose

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 Intervention Phase
Colorectal Cancer
Drug: 5-fluorouracil
Drug: leucovorin calcium
Drug: tegafur
Drug: uracil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

Primary Outcome Measures:
  • Compare the relative efficacy of UFT + LV with that of 5-FU + LV in prolonging disease-free survival and survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • evaluate the prognostic significants of proposed biomarkers, alone or in combination, in patients treated with 5-FU + LV or UFT + LV [ Designated as safety issue: No ]
  • Evaluate the relationships of various biomarkers to each other and to evaluate their association with patient and tumor characteristics [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]

Enrollment: 1608
Study Start Date: February 1997
Study Completion Date: April 2009
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
5-FU + Leucovorin
Drug: 5-fluorouracil Drug: leucovorin calcium
Experimental: Group 2
Uracil/Ftorarur + leucovorin
Drug: tegafur Drug: uracil

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00378716

Sponsors and Collaborators
National Surgical Adjuvant Breast and Bowel Project (NSABP)
Investigators
Study Chair: Michael J. O'Connell, MD Allegheny Cancer Center at Allegheny General Hospital
  More Information

Additional Information:
Publications:
O'Connell MJ, Yothers G, Paik S, et al.: Relationship between tumor gene expression and recurrence in patients with stage II/III colon cancer treated with surgery + 5-FU/LV in NSABP C-06: consistency of results with two other independent studies. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-301, 2008.
Wolmark N, Wieand S, Lembersky B, et al.: A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: results of NSABP protocol C-06. [Abstract] J Clin Oncol 22 (Suppl 14): A-3508, 247s, 2004.
Wang SJ, Zamboni BA, Wieand HS, et al.: Conditional survival for patients with colon cancer: an analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06. [Abstract] J Clin Oncol 24 (Suppl 18): A-6005, 302s, 2006.

Responsible Party: Norman Wolmark, MD, NSABP Foundation, Inc.
ClinicalTrials.gov Identifier: NCT00378716     History of Changes
Other Study ID Numbers: NSABP C-06, U10CA012027, NSABP-C-06
Study First Received: September 20, 2006
Last Updated: January 8, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):
stage II colon cancer
stage III colon cancer
adenocarcinoma of the colon

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Tegafur
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on July 28, 2014