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Clinical Trials (PDQ®)

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Clinical Trials (PDQ®)

NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Comparison of Adjuvant Low-Dose CF/5-FU vs High-Dose CF/5-FU vs Low-Dose CF/5-FU/LEV vs 5-FU/LEV Following Curative Resection in Selected Patients with Dukes' B2 and C Carcinoma of the Colon

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompletedany ageNCIEST-2288
CLB-8896, SWOG-8899, INT-0089

Objectives

I.  Compare, in a randomized Phase III intergroup setting, the efficacy of 
low-dose fluorouracil/leucovorin (5-FU/CF) vs. high-dose 5-FU/CF vs low-dose 
5-FU/CF/levamisole vs. 5-FU/levamisole in patients with Dukes' Stage B2 or C 
adenocarcinoma of the colon following curative resection.
II.  Assess independently the efficacy of each of these regimens.
III.  Assess the effect of levamisole when added to 5-FU/CF compared to 
5-FU/CF alone.


Entry Criteria

Disease Characteristics:


Histologically documented adenocarcinoma of the colon that
has undergone potentially curative en bloc surgical resection

At least 1 of the following poor prognostic indicators must
be present:

  Dukes' Stage B2 disease (i.e., transmural penetration of
  the muscular wall with penetration into or through the
  serosa) provided there is evidence of bowel obstruction
  (total or near total colonic or small bowel obstruction by
  x-ray, surgical findings, or pathology report) or
  perforation (gross operative or pathologic evidence of a
  defect in the wall of the colon with associated abscess or
  peritonitis)

  Tumor adherence to or invasion of adjacent organ(s) or
  tumor perforation but with all visible disease resected

  Dukes' Stage C disease (i.e., regional lymph node
  metastasis)

  Regional peritoneal or mesenteric implants resected en bloc

Gross inferior margin of the primary tumor must lie wholly
above the peritoneal reflection

No synchronous rectal lesions

No evidence of distant metastasis

Randomization must occur 21-35 days postoperatively
  Delay of up to 4 working days between randomization and
  initiation of treatment allowed


Prior/Concurrent Therapy:


Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy for current disease
  No prior fluorouracil at any time

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy for current disease

Surgery:
  Potentially curative en bloc resection with no gross or
  microscopic evidence of residual disease required


Patient Characteristics:


Age:
  Any age

Performance status:
  ECOG 0-2

Hematopoietic:
  WBC at least 3,500
  Platelets at least 100,000

Hepatic:
  Bilirubin no greater than 3 x ULN
  SGOT no greater than 3 x ULN
  Alkaline phosphatase no greater than 3 x ULN

Renal:
  Creatinine no greater than 3 x ULN

Other:
  Adequate oral nutrition required
  No concurrent or previous malignancy within 3 years except:
    Nonmelanomatous skin cancer
    In situ cervical cancer
  No pregnant or nursing women


Expected Enrollment

3,475 evaluable patients randomized to Arms II-IV will be studied, with 
accrual expected to be completed in mid-1992.  From September 1989 to January 
1991, patients were randomized on Arms II and III only.  Accrual on Arms IV 
and V began January 1990.

Outline

Randomized study.  Initially, Mayo/NCCTG patients were treated on NCCTG-874651 
and were randomized between only low-dose CF/5-FU and observation, while ECOG, 
SWOG, and CALGB patients were randomized across Arms I, II, and III.  Because 
analysis of data from protocol INT-0035 indicated a significant survival 
advantage for postoperative adjuvant therapy with 5-FU/levamisole in patients 
with Dukes' Stage C colon cancer, it became inappropriate to randomize these 
patients to surgery alone;  accordingly, the observation arm of this protocol 
(Arm I) was closed in September, 1989.  Accrual on Arms IV and V began in 
January, 1990.
Arm I (Arm closed September, 1989):  No further treatment.
Arm II:  Single-agent Chemotherapy with Biochemical Modulation.  
5-Fluorouracil, 5-FU, NSC-19893; Leucovorin calcium, Citrovorum Factor, CF, 
NSC-3590.  Low-dose 5-FU/CF.
Arm III:  Single-agent Chemotherapy with Biochemical Modulation.  5-FU; CF.  
High-dose 5-FU/CF.
Arm IV:  Single-agent Chemotherapy plus Biological Response Modifier Therapy.  
5-FU; plus Levamisole, LEV, NSC-177023.
Arm V:  Single-agent Chemotherapy with Drug Modulation plus Biological 
Response Modifier Therapy.  5-FU; CF; plus LEV.

Published Results

Berger AC, Sigurdson ER, LeVoyer T, et al.: Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 23 (34): 8706-12, 2005.[PUBMED Abstract]

Haller DG, Catalano PJ, Macdonald JS, et al.: Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol 23 (34): 8671-8, 2005.[PUBMED Abstract]

Le Voyer TE, Sigurdson ER, Hanlon AL, et al.: Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 21 (15): 2912-9, 2003.[PUBMED Abstract]

Meyerhardt JA, Catalano PJ, Haller DG, et al.: Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma. Cancer 98 (3): 484-95, 2003.[PUBMED Abstract]

Meyerhardt JA, Catalano PJ, Haller DG, et al.: Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21 (3): 433-40, 2003.[PUBMED Abstract]

Green RJ, Metlay JP, Propert K, et al.: Surveillance for second primary colorectal cancer after adjuvant chemotherapy: an analysis of Intergroup 0089. Ann Intern Med 136 (4): 261-9, 2002.[PUBMED Abstract]

McCollum AD, Catalano PJ, Haller DG, et al.: Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. J Natl Cancer Inst 94 (15): 1160-7, 2002.[PUBMED Abstract]

McCollum AD, Catalano PJ, Haller DG, et al.: Outcomes and toxicity in African-American and caucasian patients receiving adjuvant chemotherapy for colon cancer: a secondary analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-528, 133a, 2001.

Voyer TE, Sigurdson ER, Hanlon AL, et al.: Colon cancer survival is associated with increasing number of lymph nodes removed. A secondary analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A925, 2000.

Green RJ, Metlay JP, Propert K, et al.: Surveillance for second primary colon cancers after adjuvant chemotherapy: analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1689, 438a, 1999.

Green RJ, Metlay JP, Propert KJ, et al.: Surveilance for second primary colon cancers after adjuvant chemotherapy: analysis of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A910, 1999.

Graham RA, Wang S, Catalano PJ, et al.: Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy. Ann Surg 228 (1): 59-63, 1998.[PUBMED Abstract]

Haller DG, Catalano PJ, Macdonald JS, et al.: Fluorouracil (FU), leucovorin (LV) and levamisole (LEV) adjuvant therapy for colon cancer: five year final reportdgkin's lymphoma. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A982, 256a, 1998.

Haller DG, Catalano PJ, Macdonald JS, et al.: Fluorouracil (FU), leucovorin (LV) and levamisole (LEV) adjuvant therapy for colon cancer: four-year results of INT-0089. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-940, 265a, 1997.

Fluorouracil (FU), Leucovorin (LV), and Levamisole (LEV) adjuvant therapy for colon cancer: preliminary results of Int 0089. [Abstract] Proceedings of the American Society of Clinical Oncology 15: A486, 1996.

Related Publications

Punt CJ, Buyse M, Köhne CH, et al.: Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst 99 (13): 998-1003, 2007.[PUBMED Abstract]

Benson AB, Catalano P, Rao S, et al.: Thymidylate synthase expression as a predictor for response to 5-fluorouracil-based therapy and survival for patients with resected colon or advanced colorectal cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A917, 158a, 1997.

O'Connell MJ, Mailliard JA, Kahn MJ, et al.: Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 15 (1): 246-50, 1997.[PUBMED Abstract]

O'Connell M, Mailliard J, Macdonald J, et al.: An intergroup trial of intensive course 5FU and low dose leucovorin as surgical adjuvant therapy for high risk colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-552, 190, 1993.

Trial Contact Information

Trial Lead Organizations

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

Cancer and Leukemia Group B

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

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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