NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Comparison of MeCCNU/5-FU vs 5-FU Alone Followed by Postoperative Adjuvant Radiotherapy and Comparison of Bolus vs Continuous 5-FU as a Radioenhancer in Patients with Stages B2/3 and C1-3 Rectal Carcinoma
Basic Trial Information
|Phase III||Treatment||Completed||18 and over||MAYO-864751|
CLB-8894, EST-1288, NCCTG-864751, RTOG-8811, SWOG-8896
I. Compare, in a randomized Phase III setting, local recurrence rates, incidence of distant metastasis, disease-free survival, overall survival, and toxicity in patients who have received a potentially curative resection of modified Astler Coller Stages B2, B3, C1, C2, and C3 rectal carcinoma treated with sequential adjuvant chemotherapy plus radiotherapy using 5-fluorouracil as a radiation enhancer administered by iv bolus vs. continuous administration during radiotherapy. II. Compare the same study endpoints for the same group of patients for whom the systemic chemotherapy consists of methyl-CCNU/5-fluorouracil vs. 5-fluorouracil alone (accrual for this objective was completed as of 03/90).
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Patients aged at least 18 years with histologically documented adenocarcinoma of the rectum who have undergone a potentially curative resection with neither gross nor microscopic evidence of residual disease (in patients with adherent tumor, the margins of the resected specimen must be documented to be free of malignant cells). The surgical specimen must demonstrate an indicator of poor prognosis, i.e., the tumor must be modified Astler Coller Stage B2 or B3 (invasion of the perirectal fat or adjacent organs by direct extension) or C1, C2, or C3 (involvement of the regional lymph nodes with or without perirectal involvement). The inferior edge of the primary tumor must be at or below the sacral promontory (i.e., within the sacral hollow) or within 12 cm of the anal verge. There must be no evidence of distant metastasis and no regional metastasis that cannot be resected en bloc with the primary lesion. Patients with ovarian metastasis are ineligible unless the ovary is involved by direct invasion and is resected en bloc with the primary. There must be no extension of malignant disease to or below the dentate line. There may have been no prior chemotherapy or radiotherapy of the pelvis. Patients must be entered 21-70 days postoperatively, must have recovered from the acute effects of surgery, and must be maintaining normal oral nutrition. Hematopoietic function must be adequate, and patients must be free from any active and significant coexisting disease that would preclude protocol chemotherapy and radiotherapy. There may have been no previous cancer of the colon or rectum unless the patient has undergone complete surgical resection at least 5 years prior to entry and has been free from evidence of recurrence. There may be no synchronous extra pelvic primary colon cancer unless it is modified Astler Coller Stage A or B1 (no tumor penetration beyond the muscularis propria) and has been totally resected. There may have been no malignant disease other than superficial squamous or basal cell skin cancer or in-situ carcinoma of the cervix during the 5 years prior to entry. Pregnancy and lactation exclude. The institution at which radiotherapy is to be administered must have a linear accelerator with a minimum energy of 4 MeV and a simulator that duplicates the geometry of the actual treatment machine and is capable of producing films of diagnostic quality.
450 patients will be entered over about 4.5 years. As of 03/90, the original accrual objective had been met. After this date, up to 200 additional patients will be randomized between Arms III and IV only.
Randomized study. As of 03/90, patients are randomized on Arms III and IV only. Arm I (Arm closed 03/90): 2-Drug Combination Chemotherapy followed by Radiotherapy with Radiosensitization followed by 2-Drug Combination Chemotherapy. Methyl-CCNU, MeCCNU, NSC-95441; 5-Fluorouracil, 5-FU, NSC-19893; followed by pelvic irradiation using linear accelerators with minimum energies of 4 MeV plus radiation enhancement with 5-FU; followed by MeCCNU; 5-FU. Bolus 5-FU during Radiotherapy. Arm II (Arm closed 03/90): 2-Drug Combination Chemotherapy followed by Radiotherapy with Radiosensitization followed by 2-Drug Combination Chemotherapy. Systemic Chemotherapy with MeCCNU/5-FU and Radiotherapy as in Arm I. Continuous 5-FU during Radiotherapy. Arm III: Single-agent Chemotherapy followed by Radiotherapy with Radiosensitization followed by Single-agent Chemotherapy. 5-FU; followed by Radiotherapy as in Arm I; followed by 5-FU. Bolus 5-FU during Radiotherapy. Arm IV: Single-agent Chemotherapy followed by Radiotherapy with Radiosensitization followed by Single-agent Chemotherapy. Systemic Chemotherapy with 5-FU and Radiotherapy as in Arm III. Continuous 5-FU during Radiotherapy.
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]
O'Connell M, Martenson J, Rich T, et al.: Protracted venous infusion (PVI) 5-fluorouracil (5FU) as a component of effective combined modality postoperative surgical adjuvant therapy for high-risk rectal cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-564, 193, 1993.
O'Connell M, Wieand H, Krook J, et al.: Lack of value for methyl-CCNU (MeCCNU) as a component of effective rectal cancer surgical adjuvant therapy: interim analysis of intergroup protocol 86-47-51. [Abstract] Proceedings of the American Society of Clinical Oncology 10: A-403, 134, 1991.
Garrity MM, Burgart LJ, Mahoney MR, et al.: Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a North Central Cancer Treatment Group Study. J Clin Oncol 22 (9): 1572-82, 2004.[PUBMED Abstract]
Gunderson LL, Sargent DJ, Tepper JE, et al.: Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 22 (10): 1785-96, 2004.[PUBMED Abstract]
Gunderson LL, Sargent DJ, Tepper JE, et al.: Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis. Int J Radiat Oncol Biol Phys 54 (2): 386-96, 2002.[PUBMED Abstract]
O'Connell MJ, Martenson JA, Wieand HS, et al.: Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331 (8): 502-7, 1994.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Mayo Clinic Cancer Center
North Central Cancer Treatment Group
Ph: 218-786-8364; 888-203-7267
Radiation Therapy Oncology Group
Cancer and Leukemia Group B
Ph: 617-632-3474; 866-790-4500
Eastern Cooperative Oncology Group
Southwest Oncology Group
Ph: 212-604-6011; 888-442-2623
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.