Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Fluorouracil and Leucovorin and/or Levamisole After Surgery In Treating Patients With Dukes' B Or Dukes' C Colon Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	under 71	NCI	NSABP-C-04 NCOG-NSABP-C-04, NCT00425152

Objectives

I.  Compare, in a Phase III setting, disease-free survival and overall 
survival of patients who have undergone potentially curative resection of 
Dukes' B or C carcinoma of the colon randomly assigned to adjuvant therapy 
with 5-fluorouracil/leucovorin vs. 5-fluorouracil/levamisole vs. 
5-fluorouracil/leucovorin/levamisole.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients under the age of 71 years at 
the time of potentially curative surgery for histologically documented Dukes' 
B or C carcinoma of the colon, provided no more than 42 days have intervened 
between surgery and initiation of adjuvant therapy.  The full extent of tumor 
must be clearly defined by palpation without having to open the pelvic 
peritoneum to be classified as a primary tumor of the colon.  Dukes' B disease 
is defined as tumor that has invaded the wall of the colon with extension to 
pericolic tissue but without involvement of lymph nodes, and Dukes' C disease 
is defined as invasion of the wall of the colon to any depth with extension to 
regional lymph nodes.  Patients may have more than one synchronous primary 
colon tumor, in which case the stage of the more advanced tumor will be used 
for this protocol; presence of concurrent rectal cancer excludes.  Patients 
with intestinal obstruction are eligible, and preliminary or complementary 
colostomy does not preclude entry.  The presence of free perforation 
manifested by free air in the abdomen excludes, but patients with walled off 
perforations are eligible.  If adjacent structures (e.g., bladder, small 
intestine, ovary) involved by direct extension of tumor were removed en bloc, 
the patient is eligible only if the surgical margins are histologically 
negative for tumor and it is the judgment of the surgeon that the resection 
was curative; the presence of noncontiguous intra-abdominal metastases, even 
if resected, renders a patient ineligible.  Patients may have experienced 
postoperative complications as long as they are able to start therapy within 
42 days.  The CEA must be determined postoperatively (preoperative CEA is 
optional), but the results need not be known prior to randomization.  There 
may have been no prior treatment for the current malignancy other than 
surgical resection.  The postoperative WBC must be at least 4,000 and 
platelets at least 100,000, and adequate hepatic and renal function must be 
documented by the following parameters:  total bilirubin not greater than 1.5 
mg/dl, SGOT or SGPT not greater than 60 IU/ml, and serum creatinine not 
greater than 1.5 mg/dl.  The performance status must be 0-2, and patients must 
be free from nonmalignant systemic disease (cardiovascular, renal, hepatic, 
etc.) that would preclude protocol chemotherapy.  Aside from squamous and 
basal cell carcinoma of the skin and carcinoma in situ of the cervix, there 
may be no previous or concomitant second malignancy.  Pregnancy excludes.

Expected Enrollment

1,800 evaluable patients will be accrued over about 3 years; an additional 2 
years will be required before final analysis.

Outline

Randomized study.
Arm I:  Single-agent Chemotherapy with Drug Modulation.  5-Fluorouracil, 5-FU, 
NSC-19893; with Leucovorin calcium, Citrovorum Factor, CF, NSC-3590.
Arm II:  Single-agent Chemotherapy with Drug Modulation plus Biological 
Response Modifier Therapy.  5-FU; with CF; plus Levamisole, LEV, NSC-177023.
Arm III:  Single-agent Chemotherapy plus Biological Response Modifier Therapy. 
 5-FU; plus LEV.

Wolmark N, Rockette H, Mamounas E, et al.: Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol 17 (11): 3553-9, 1999.[PUBMED Abstract]

Wolmark N, Rockette H, Mamounas EP, et al.: The relative efficacy of 5-FU + leucovorin (FU-LV), 5-FU + levamisole (FU-LEV), and 5-FU + leucovorin + levamisole (FU-LV-LEV) in patients with Dukes' B and C carcinoma of the colon: first report of NSABP C-04. [Abstract] Proceedings of the American Society of Clinical Oncology 15: A460, 205a, 1996.

Wilkinson NW, Yothers G, Lopa SH, et al.: Long-term survival results of surgery alone compared with surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP adjuvant trials C-01 through C-05. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-442, 2009.

Kim GP, Colangelo LH, Wieand HS, et al.: Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol 25 (7): 767-72, 2007.[PUBMED Abstract]

Dignam JJ, Polite BN, Yothers G, et al.: Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst 98 (22): 1647-54, 2006.[PUBMED Abstract]

Wang SJ, Zamboni BA, Wieand HS, et al.: Conditional survival for patients with colon cancer: an analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06. [Abstract] J Clin Oncol 24 (Suppl 18): A-6005, 302s, 2006.

Kim GP, Colangelo L, Wieand H, et al.: Prognostic and predictive roles of high-degree microsatellite instability (MSI-H) in colon cancer: National Cancer Institute (NCI)-National Surgical Adjuvant Bowel Project (NSABP) collaborative study. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-227, 2005.

Allegra CJ, Paik S, Colangelo LH, et al.: Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. J Clin Oncol 21 (2): 241-50, 2003.[PUBMED Abstract]

Wolmark N, Colangelo L, Wieand S: National Surgical Adjuvant Breast and Bowel Project trials in colon cancer. Semin Oncol 28 (1 Suppl 1): 9-13, 2001.[PUBMED Abstract]

Dignam JJ, Colangelo L, Tian W, et al.: Outcomes among African-Americans and Caucasians in colon cancer adjuvant therapy trials: findings from the National Surgical Adjuvant Breast and Bowel Project. J Natl Cancer Inst 91 (22): 1933-40, 1999.[PUBMED Abstract]

Mamounas E, Wieand S, Wolmark N, et al.: Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04) J Clin Oncol 17 (5): 1349-55, 1999.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Norman Wolmark, MD, Protocol chair		Ph: 412-359-3336; 866-680-0004

Clinical Research Program - Northern California Cancer Center

Robert Carlson, MD, Protocol chair		Ph: 650-725-6457; 800-756-9000

Registry Information
Official Title		A Clinical Trial to Assess the Relative Efficacy of 5-FU + Leucovorin, 5-FU + Levamisole, and 5-FU + Leucovorin + Levamisole in Patients with Dukes' B and C Carcinoma of the Colon
Registered in ClinicalTrials.gov		NCT00425152 1
Date Submitted to PDQ		1990-12-31
Information Last Verified		2009-03-26

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00425152