NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Comparison of Adjuvant Low-Dose CF/5-FU vs High-Dose CF/5-FU vs Low-Dose CF/5-FU/LEV vs 5-FU/LEV Following Curative Resection in Selected Patients with Dukes' B2 and C Carcinoma of the Colon
Basic Trial Information
|Phase III||Treatment||Completed||any age||NCI||EST-2288|
CLB-8896, SWOG-8899, INT-0089
I. Compare, in a randomized Phase III intergroup setting, the efficacy of low-dose fluorouracil/leucovorin (5-FU/CF) vs. high-dose 5-FU/CF vs low-dose 5-FU/CF/levamisole vs. 5-FU/levamisole in patients with Dukes' Stage B2 or C adenocarcinoma of the colon following curative resection. II. Assess independently the efficacy of each of these regimens. III. Assess the effect of levamisole when added to 5-FU/CF compared to 5-FU/CF alone.
Histologically documented adenocarcinoma of the colon that has undergone potentially curative en bloc surgical resection At least 1 of the following poor prognostic indicators must be present: Dukes' Stage B2 disease (i.e., transmural penetration of the muscular wall with penetration into or through the serosa) provided there is evidence of bowel obstruction (total or near total colonic or small bowel obstruction by x-ray, surgical findings, or pathology report) or perforation (gross operative or pathologic evidence of a defect in the wall of the colon with associated abscess or peritonitis) Tumor adherence to or invasion of adjacent organ(s) or tumor perforation but with all visible disease resected Dukes' Stage C disease (i.e., regional lymph node metastasis) Regional peritoneal or mesenteric implants resected en bloc Gross inferior margin of the primary tumor must lie wholly above the peritoneal reflection No synchronous rectal lesions No evidence of distant metastasis Randomization must occur 21-35 days postoperatively Delay of up to 4 working days between randomization and initiation of treatment allowed
Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for current disease No prior fluorouracil at any time Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for current disease Surgery: Potentially curative en bloc resection with no gross or microscopic evidence of residual disease required
Age: Any age Performance status: ECOG 0-2 Hematopoietic: WBC at least 3,500 Platelets at least 100,000 Hepatic: Bilirubin no greater than 3 x ULN SGOT no greater than 3 x ULN Alkaline phosphatase no greater than 3 x ULN Renal: Creatinine no greater than 3 x ULN Other: Adequate oral nutrition required No concurrent or previous malignancy within 3 years except: Nonmelanomatous skin cancer In situ cervical cancer No pregnant or nursing women
3,475 evaluable patients randomized to Arms II-IV will be studied, with accrual expected to be completed in mid-1992. From September 1989 to January 1991, patients were randomized on Arms II and III only. Accrual on Arms IV and V began January 1990.
Randomized study. Initially, Mayo/NCCTG patients were treated on NCCTG-874651 and were randomized between only low-dose CF/5-FU and observation, while ECOG, SWOG, and CALGB patients were randomized across Arms I, II, and III. Because analysis of data from protocol INT-0035 indicated a significant survival advantage for postoperative adjuvant therapy with 5-FU/levamisole in patients with Dukes' Stage C colon cancer, it became inappropriate to randomize these patients to surgery alone; accordingly, the observation arm of this protocol (Arm I) was closed in September, 1989. Accrual on Arms IV and V began in January, 1990. Arm I (Arm closed September, 1989): No further treatment. Arm II: Single-agent Chemotherapy with Biochemical Modulation. 5-Fluorouracil, 5-FU, NSC-19893; Leucovorin calcium, Citrovorum Factor, CF, NSC-3590. Low-dose 5-FU/CF. Arm III: Single-agent Chemotherapy with Biochemical Modulation. 5-FU; CF. High-dose 5-FU/CF. Arm IV: Single-agent Chemotherapy plus Biological Response Modifier Therapy. 5-FU; plus Levamisole, LEV, NSC-177023. Arm V: Single-agent Chemotherapy with Drug Modulation plus Biological Response Modifier Therapy. 5-FU; CF; plus LEV.
Berger AC, Sigurdson ER, LeVoyer T, et al.: Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 23 (34): 8706-12, 2005.[PUBMED Abstract]
Haller DG, Catalano PJ, Macdonald JS, et al.: Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol 23 (34): 8671-8, 2005.[PUBMED Abstract]
Le Voyer TE, Sigurdson ER, Hanlon AL, et al.: Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 21 (15): 2912-9, 2003.[PUBMED Abstract]
Meyerhardt JA, Catalano PJ, Haller DG, et al.: Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer 98 (3): 484-95, 2003.[PUBMED Abstract]
Meyerhardt JA, Catalano PJ, Haller DG, et al.: Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21 (3): 433-40, 2003.[PUBMED Abstract]
Green RJ, Metlay JP, Propert K, et al.: Surveillance for second primary colorectal cancer after adjuvant chemotherapy: an analysis of Intergroup 0089. Ann Intern Med 136 (4): 261-9, 2002.[PUBMED Abstract]
McCollum AD, Catalano PJ, Haller DG, et al.: Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. J Natl Cancer Inst 94 (15): 1160-7, 2002.[PUBMED Abstract]
McCollum AD, Catalano PJ, Haller DG, et al.: Outcomes and toxicity in African-American and caucasian patients receiving adjuvant chemotherapy for colon cancer: a secondary analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-528, 133a, 2001.
Voyer TE, Sigurdson ER, Hanlon AL, et al.: Colon cancer survival is associated with increasing number of lymph nodes removed. A secondary analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A925, 2000.
Green RJ, Metlay JP, Propert K, et al.: Surveillance for second primary colon cancers after adjuvant chemotherapy: analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1689, 438a, 1999.
Green RJ, Metlay JP, Propert KJ, et al.: Surveilance for second primary colon cancers after adjuvant chemotherapy: analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A910, 1999.
Graham RA, Wang S, Catalano PJ, et al.: Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy. Ann Surg 228 (1): 59-63, 1998.[PUBMED Abstract]
Haller DG, Catalano PJ, Macdonald JS, et al.: Fluorouracil (FU), leucovorin (LV) and levamisole (LEV) adjuvant therapy for colon cancer: five year final reportdgkin's lymphoma. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A982, 256a, 1998.
Haller DG, Catalano PJ, Macdonald JS, et al.: Fluorouracil (FU), leucovorin (LV) and levamisole (LEV) adjuvant therapy for colon cancer: four-year results of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-940, 265a, 1997.
Fluorouracil (FU), Leucovorin (LV), and Levamisole (LEV) adjuvant therapy for colon cancer: preliminary results of Int 0089. [Abstract] Proceedings of the American Society of Clinical Oncology 15: A486, 1996.
Punt CJ, Buyse M, Köhne CH, et al.: Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst 99 (13): 998-1003, 2007.[PUBMED Abstract]
Benson AB, Catalano P, Rao S, et al.: Thymidylate synthase expression as a predictor for response to 5-fluorouracil-based therapy and survival for patients with resected colon or advanced colorectal cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A917, 158a, 1997.
O'Connell MJ, Mailliard JA, Kahn MJ, et al.: Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 15 (1): 246-50, 1997.[PUBMED Abstract]
O'Connell M, Mailliard J, Macdonald J, et al.: An intergroup trial of intensive course 5FU and low dose leucovorin as surgical adjuvant therapy for high risk colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-552, 190, 1993.
Trial Contact Information
Trial Lead Organizations
Eastern Cooperative Oncology Group
Southwest Oncology Group
Ph: 212-604-6011; 888-442-2623
Cancer and Leukemia Group B
Ph: 617-632-3474; 866-790-4500
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.