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Clinical Trials (PDQ®)

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Clinical Trials (PDQ®)

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
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted18 and overMAYO-864751
CLB-8894, EST-1288, NCCTG-864751, RTOG-8811, SWOG-8896

Objectives

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).

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

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.

Expected Enrollment

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.

Outline

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.

Published Results

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.

Related Publications

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

Michael O'Connell, MD, Protocol chair (Contact information may not be current)
Ph: 507-284-2511

North Central Cancer Treatment Group

James Krook, MD, Protocol chair
Ph: 218-786-8364; 888-203-7267
Email: jkrook@smdc.org

Radiation Therapy Oncology Group

Leonard Gunderson, MD, Protocol chair
Ph: 480-301-7351
Email: gunderson.leonard@mayo.edu

Cancer and Leukemia Group B

Robert Mayer, MD, FACP, Protocol chair
Ph: 617-632-3474; 866-790-4500

Eastern Cooperative Oncology Group

Daniel Haller, MD, Protocol chair
Ph: 215-662-6318

Southwest Oncology Group

John MacDonald, MD, Protocol chair
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.

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