Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed 18 and over NCI NCCTG-874651 MAYO-874651, MDA-DM-89021, NCCTG-87-46-51

Objectives

I.  Compare survival and disease-free interval of patients with Dukes' Stages 
B2 and C adenocarcinoma of the colon randomly assigned to treatment with 
5-fluorouracil plus low-dose folinic acid as adjuvant chemotherapy vs. no 
adjuvant therapy following complete surgical resection.
II.  Compare survival and disease-free interval of patients with Dukes' Stages 
B2, C, and D adenocarcinoma of the colon randomly assigned to biological 
response modifier therapy with recombinant interferon gamma (IFN-G) as 
adjuvant therapy vs. no adjuvant therapy following complete surgical resection.
III.  Determine the effect of adjuvant IFN-G vs. no adjuvant therapy on 
selected laboratory assays of immune function in patients who have undergone 
complete resection of adenocarcinoma of the colon.
IV.  Evaluate the correlation of alterations in immune parameters with 
survival in this patient population.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients aged 18 years and older with 
histologically proven adenocarcinoma of the colon who have undergone resection 
of their tumors with neither macroscopic nor microscopic evidence of residual 
disease provided they fall into one of several poor-risk categories.  Dukes' 
Stage B patients must have one of the following poor-prognosis indicators:  
transmural penetration of tumor into or through the serosa with intestinal 
obstruction and/or perforation; transmural penetration of tumor through the 
serosa with adherence to or invasion of adjacent organ(s) or structure(s) with 
all malignant disease resected en bloc; or transmural penetration through the 
serosa with regional tumor implants involving adjacent mesentery, omentem, or 
peritoneum with all malignant disease resected en bloc.  Duke's Stage C 
patients will have regional lymph node involvement with or without colon 
perforation, obstruction, or involvement of adjacent organ(s) or structure(s) 
with all malignant disease resected en bloc.  Duke's Stage D patients are 
eligible if they fulfill one of the following conditions:  completely resected 
nodal, mesenteric, omental, or peritoneal metastasis not removed in direct 
continuity with the primary tumor resection; completely resected distant 
abdominal metastasis (e.g., ovarian, hepatic, peritoneal) detected at the time 
of primary surgery, provided all known and suspected areas of malignant 
disease are resected; or completely resected distant abdominal metastasis 
noted as recurrent disease at any time following primary colon resection, 
provided all known and suspected areas of malignant disease are resected.  The 
primary tumor must extend above the peritoneal reflection and the gross 
inferior (i.e., caudad) margin of the primary tumor must lie completely above 
the peritoneal reflection.  Patients with rectal adenocarcinoma whose inferior 
tumor margin is at or below the peritoneal reflection are ineligible.  
Randomization should take place between 21 and 30 days postoperatively.  The 
ECOG performance status must be 0-2 (at least 50% of the day ambulatory), and 
patients must be maintaining adequate oral nutrition.  Pregnant and lactating 
women are excluded, and women of childbearing potential and fertile men must 
agree to use effective contraception during treatment.  Adequate hematologic 
reserves must be evidenced by a WBC of at least 3,500 and platelets of at 
least 100,000.  Dukes' D patients with heart disease (myocardial infarction 
within 3 months or history of CHF), CNS disease of any kind past or present, 
or liver disease (SGOT more than twice the upper limit of institutional normal 
or evidence of chronic liver disease) are ineligible.  Dukes' B2 and C 
patients with heart disease, CNS disease, or liver disease are not eligible 
for randomization to interferon gamma.  There may have been no prior 
radiotherapy or chemotherapy for colon cancer and no prior exposure to 
5-fluorouracil; concurrent radiotherapy, chemotherapy, and corticosteroid 
therapy are not allowed.  There may be no concurrent second malignancy and no 
previous malignant tumor within 3 years of entry other than superficial 
squamous or basal cell carcinoma of the skin and carcinoma in situ of the 
cervix.  Treatment should be initiated within 4 days of randomization.

Expected Enrollment

Initially, Dukes' B and C patients will be randomized on all three arms and 
Dukes' D patients will be randomized on Arms I and II.  After 125 patients 
have been accrued on Arm II, Dukes' B and C patients will continue to be 
randomized on Arms I and III if this component of the protocol remains open.  
The comparison of 5-FU/CF is part of an intergroup study (including 
NCCTG/Mayo, M.D. Anderson, SWOG, ECOG, and CALGB), for which the total accrual 
goal is 800 patients over about 2 years.  For reporting purposes, Duke's B2 
and C patients randomized to Arms I and III will officially be participants in 
the intergroup study (INT-0089).  It is anticipated that 2.5 years will be 
required for completion of accrual to Arm II.

Outline

Randomized study.  Patients with Dukes' B2 and C disease who do not have 
heart, CNS, or liver disease are randomized on Arms I, II, and III, while 
those with heart, CNS, or liver disease are randomized on Arms I and III only. 
 Dukes' Stage D patients (all of whom must not have heart, CNS, or liver 
disease) are randomized on Arms I and II only.
Arm I:  Control.  No postoperative adjuvant therapy.
Arm II:  Biological Response Modifier Therapy.  Human Recombinant Gamma 
Interferon, IFN-G, NSC-600662.
Arm III:  Single-agent Chemotherapy with Biochemical Modulation.  
5-Fluorouracil, 5-FU, NSC-19893; plus Folinic Acid, Citrovorum Factor, CF, 
NSC-3590.

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]

Wiesenfeld M, O'Connell MJ, Wieand HS, et al.: Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer. J Clin Oncol 13 (9): 2324-9, 1995.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Martin Wiesenfeld, MD, Protocol chair		Ph: 319-363-8303

Mayo Clinic Cancer Center

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

M. D. Anderson Cancer Center at University of Texas

Richard Pazdur, MD, Protocol chair		Ph: 301-594-2473