NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Comparison of Four Systemic Regimens Combined with Pelvic Irradiation as Adjuvant Therapy for Totally Resected Stage II/III Adenocarcinoma of the Rectum: 5-FU vs 5-FU/CF vs 5-FU/LEV vs 5-FU/CF/LEV
Basic Trial Information
|Phase III||Treatment||Closed||over 18||NCI||CLB-9081|
CAN-NCIC-CO6, EST-4290, NCCTG-904751, RTOG-9014, SWOG-9040, INT-0114, CO6
I. Compare, in a Phase III Intergroup setting, local recurrence rates, probability of distant metastases, disease-free survival, and overall survival of patients with totally resected adenocarcinoma of the rectum randomly assigned to one of four systemic regimens, each combined with the same regimen of pelvic irradiation: fluorouracil alone vs. fluorouracil/leucovorin vs. fluorouracil/levamisole vs. fluorouracil/leucovorin/levamisole.
Histologically documented adenocarcinoma of the rectum that has undergone potentially curative en bloc resection with neither gross nor microscopic evidence of disease Resection margins must be negative in case of adherent tumor Poor prognosis must be indicated by either of the following: Pathologic evidence of extension through the muscularis propria into the subserosa or into nonperitonealized pericolic or perirectal tissue Pathologically proven regional nodal involvement, i.e., modified Astler-Coller Stage B2, B3, or C or TNM Stage T3N0, T4N0, or N1-3 No evidence of distant metastasis, including even grossly resected peritoneal metastases Tumor must be of rectal and not colonic origin, i.e.,: Lower edge of the tumor mass must be below the peritoneal reflection, or a portion of the tumor must be defined as being retroperitoneal by the surgeon If the lower margin of the tumor is within 12 cm of the anal verge on proctoscopic examination, the tumor is defined as being of rectal origin unless it is found to lie entirely above the peritoneal reflection at surgery Tumor extension to the dentate line or below excludes No synchronous colon cancer allowed other than completely resected modified Astler-Coller Stage A or B1 (TNM Stage I, no nodal involvement or penetration beyond the muscularis propria)
Biologic therapy: No prior immunotherapy Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the pelvis Surgery: 3-10 weeks since definitive surgery Recovery from surgery required
Age: Over 18 Performance status: CALGB (Zubrod) 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 130,000 Hepatic: Not specified Renal: Not specified Other: Adequate oral nutrition required No serious medical illness that would preclude protocol therapy No psychiatric condition that would preclude informed consent No active second malignancy within previous 5 years except: Nonmelanomatous skin cancer In situ cervical cancer No pregnant or lactating women Treatment must begin within 10 days of randomization
1,752 patients will be entered in less than 4 years.
Randomized study. Arm I: Single-agent Chemotherapy followed by Radiotherapy with Radiosensitization followed by Single-agent Chemotherapy. Fluorouracil, 5-FU, NSC-19893; followed by pelvic irradiation using linear accelerators with minimum energies of 4 MeV; with 5-FU; followed by 5-FU. Arm II: Single-agent Chemotherapy with Drug Modulation followed by Radiotherapy with Radiosensitization followed by Single-agent Chemotherapy with Drug Modulation. 5-FU; with Leucovorin calcium, Citrovorum Factor, CF, NSC-3590; followed by pelvic irradiation as in Arm I; with 5-FU and CF; followed by 5-FU; with CF. Arm III: Single-agent Chemotherapy plus Biological Response Modifier Therapy followed by Radiotherapy with Radiosensitization followed by Single-agent Chemotherapy plus Biological Response Modifier Therapy. 5-FU; plus Levamisole, LEV, NSC-177023; followed by pelvic irradiation as in Arm I; with 5-FU; followed by 5-FU; plus LEV. Arm IV: Single-agent Chemotherapy with Drug Modulation plus Biological Response Modifier Therapy followed by Radiotherapy with Radiosensitization followed by Single-agent Chemotherapy with Drug Modulation plus Biological Response Modifier Therapy. 5-FU; with CF; plus LEV; followed by pelvic irradiation as in Arm I; with 5-FU and CF; followed by 5-FU; with CF; plus LEV.
Meyers MO, Hollis DR, Mayer RJ, et al.: Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: an analysis of Intergroup 0114. [Abstract] J Clin Oncol 25 (Suppl 18): A-4006, 2007.
Meyerhardt JA, Tepper JE, Niedzwiecki D, et al.: Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114. J Clin Oncol 22 (4): 648-57, 2004.[PUBMED Abstract]
Meyerhardt JA, Tepper JE, Niedzwiecki D, et al.: Impact of hospital procedure volume on surgical operation and long-term outcomes in high-risk curatively resected rectal cancer: findings from the Intergroup 0114 Study. J Clin Oncol 22 (1): 166-74, 2004.[PUBMED Abstract]
Miller RC, Sargent DJ, Martenson JA, et al.: Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial. Int J Radiat Oncol Biol Phys 54 (2): 409-13, 2002.[PUBMED Abstract]
Tepper JE, O'Connell M, Donna H, et al.: Analysis of surgical salvage after failure of primary therapy in rectal cancer: results from INT 0114. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-507, 2002.
Tepper JE, O'Connell M, Niedzwiecki D, et al.: Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol 20 (7): 1744-50, 2002.[PUBMED Abstract]
Tepper JE, O'Connell MJ, Niedzwiecki D, et al.: Final report of INT 0114: adjuvant therapy in rectal cancer: analysis by treatment, stage and gender. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-489, 123a, 2001.
Tepper JE, O'Connell MJ, Niedzwiecki D, et al.: Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19 (1): 157-63, 2001.[PUBMED Abstract]
Tepper JE, O'Connell MJ, Petroni GR, et al.: Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol 15 (5): 2030-9, 1997.[PUBMED Abstract]
Tepper J, O'Connell M, Petroni G, et al.: Toxicity in the adjuvant therapy of rectal cancer: a preliminary report of Intergroup 0114 (CALGB 9081). [Abstract] Proceedings of the American Society of Clinical Oncology 15: A-481, 210a, 1996.
Stocchi L, Nelson H, Sargent DJ, et al.: Impact of surgical and pathologic variables in rectal cancer: a United States community and cooperative group report. J Clin Oncol 19 (18): 3895-902, 2001.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Radiation Therapy Oncology Group
Southwest Oncology Group
Ph: 212-604-6011; 888-442-2623
North Central Cancer Treatment Group
NCIC-Clinical Trials Group
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.