Back to resultsCombination Chemotherapy in Treating Patients With Resected Colon Cancer
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
5-fluorouracil
leucovorin calcium
tegafur
uracil
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Group 1
Group 2
Arm Description
5-FU + Leucovorin
Uracil/Ftorarur + leucovorin
Outcomes
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
Full Information
NCT ID
NCT00378716
First Posted
September 20, 2006
Last Updated
January 8, 2010
Sponsor
NSABP Foundation Inc
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00378716
Brief Title
Combination Chemotherapy in Treating Patients With Resected Colon Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
January 2010
Overall Recruitment Status
Completed
Study Start Date
February 1997 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
NSABP Foundation Inc
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1608 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Active Comparator
Arm Description
5-FU + Leucovorin
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Uracil/Ftorarur + leucovorin
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Type
Drug
Intervention Name(s)
tegafur
Intervention Type
Drug
Intervention Name(s)
uracil
Primary Outcome Measure Information:
Title
Compare the relative efficacy of UFT + LV with that of 5-FU + LV in prolonging disease-free survival and survival
Secondary Outcome Measure Information:
Title
evaluate the prognostic significants of proposed biomarkers, alone or in combination, in patients treated with 5-FU + LV or UFT + LV
Title
Evaluate the relationships of various biomarkers to each other and to evaluate their association with patient and tumor characteristics
Title
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
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael J. O'Connell, MD
Organizational Affiliation
Allegheny Cancer Center at Allegheny General Hospital
Official's Role
Study Chair
12. IPD Sharing Statement
Citations:
PubMed Identifier
17060221
Citation
Soran A, Nesbitt L, Mamounas EP, Lembersky B, Bryant J, Anderson S, Brown A, Passarello M. Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience. Clin Trials. 2006;3(5):478-85. doi: 10.1177/1740774506070747.
Results Reference
background
Citation
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.
Results Reference
background
PubMed Identifier
11273592
Citation
Wolmark N, Colangelo L, Wieand S. National Surgical Adjuvant Breast and Bowel Project trials in colon cancer. Semin Oncol. 2001 Feb;28(1 Suppl 1):9-13. doi: 10.1016/s0093-7754(01)90245-3.
Results Reference
background
Citation
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.
Results Reference
result
PubMed Identifier
17264338
Citation
Kopec JA, Yothers G, Ganz PA, Land SR, Cecchini RS, Wieand HS, Lembersky BC, Wolmark N. Quality of life in operable colon cancer patients receiving oral compared with intravenous chemotherapy: results from National Surgical Adjuvant Breast and Bowel Project Trial C-06. J Clin Oncol. 2007 Feb 1;25(4):424-30. doi: 10.1200/JCO.2005.05.2597. Erratum In: J Clin Oncol. 2007 Dec 1;25(34):5540-1.
Results Reference
result
PubMed Identifier
16648506
Citation
Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006 May 1;24(13):2059-64. doi: 10.1200/JCO.2005.04.7498.
Results Reference
result
PubMed Identifier
16945170
Citation
Soran A, Harlak A, Wilson JW, Nesbitt L, Lembersky BC, Wienad HS, O'Connell MJ. Diverticular disease in patients with colon cancer: subgroup analysis of national surgical adjuvant breast and bowel project protocol C-06. Clin Colorectal Cancer. 2006 Jul;6(2):140-5. doi: 10.3816/ccc.2006.n.031.
Results Reference
result
Citation
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.
Results Reference
result
PubMed Identifier
11098486
Citation
Smith RE, Lembersky BC, Wieand HS, Colangelo L, Mamounas EP. UFT/leucovorin vs 5-FU/leucovorin in colon cancer. Oncology (Williston Park). 2000 Oct;14(10 Suppl 9):24-7.
Results Reference
result
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Combination Chemotherapy in Treating Patients With Resected Colon Cancer
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