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

Alternate Title

Combination Chemotherapy in Treating Patients With Stage III Colon Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed 18 and over NCI CLB-89803 CAN-NCIC-CO15, E-89803, NCCTG-C89803, SWOG-C89803, NCT00003835, C89803, CO15

Objectives

I. Compare the overall and disease free survival of patients with stage III 
colon cancer treated with adjuvant fluorouracil and leucovorin calcium with or 
without irinotecan.

II. Assess prognostic markers and correlate their expression with disease free 
and overall survival of these patients.

III. Assess the influence of diet, body mass index, and physical activity on 
the risk of cancer recurrence and survival in these patients.

IV. Assess the influence of diet, obesity, and physical activity on the risk 
of toxicity associated with adjuvant therapy in these patients. 

V. Determine whether pathological features (including tumor grade, tumor 
mitotic (proliferation) index, tumor border configuration, and host lymphoid 
response to tumor; and lymphatic vessel, venous vessel and perineural 
invasion) predict outcome in this patient population. 

Entry Criteria

Disease Characteristics:

Histologically proven stage III (Tx, N1-2, M0) adenocarcinoma of the colon
 Gross inferior (caudal) margin of primary tumor must be above the peritoneal
  reflection
 Completely resected with negative radial resecting margins

No distant metastatic disease

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 No prior chemotherapy for colon cancer
 No other concurrent chemotherapy

Endocrine therapy:
 No concurrent hormone therapy except:
  Steroids for adrenal failure
  Hormones for nondisease related conditions (e.g., diabetes)
  Intermittent dexamethasone as an antiemetic

Radiotherapy:
 No prior radiotherapy for colon cancer

Surgery:
 See Disease Characteristics

Patient Characteristics:

Age:
 18 and over

Performance status:
 Zubrod 0-2

Life expectancy:
 Not specified

Hematopoietic:
 Granulocyte count at least 1,500/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin no greater than upper limit of normal (ULN)

Renal:
 Creatinine no greater than 1.5 times ULN

Other:
 No other prior or concurrent malignancy within the past 5 years except
  adequately treated basal cell or squamous cell skin cancer or carcinoma in
  situ of the cervix
 Not pregnant or nursing
 Fertile patients must use effective contraception

Expected Enrollment

A total of 1260 patients will be accrued for this study within 3 years.

Outline

This is a randomized, multicenter study.  Patients are stratified according to 
lymph node involvement (1-3 vs 4 or more), histology (poorly differentiated or 
undifferentiated vs well or moderately differentiated), and preoperative serum 
CEA (less than 5.0 ng/mL vs at least 5.0 ng/mL vs unknown).

Study therapy must begin within 21-56 days after surgery.  Patients are 
randomized to one of two treatment arms:

Arm I:  Patients receive leucovorin calcium IV over 2 hours and fluorouracil 
IV beginning 1 hour into leucovorin calcium infusion weekly for 6 weeks.  
Treatment is repeated every 8 weeks for 4 courses.

Arm II:  Patients receive irinotecan IV over 90 minutes, followed by 
leucovorin calcium IV, then followed by fluorouracil IV weekly for 4 weeks.  
Treatment is repeated every 6 weeks for 5 courses.

Patients complete a food questionnaire at the beginning of the third course 
and then at 6 months after study therapy. 

Patients are followed every 3 months for 2 years, every 4 months for 2 years, 
then annually thereafter.

Chan JA, Meyerhardt JA, Niedzwiecki D, et al.: Association of family history with cancer recurrence and survival among patients with stage III colon cancer. JAMA 299 (21): 2515-23, 2008.[PUBMED Abstract]

Jackson NA, Fuchs CS, Niedzwiecki D, et al.: The impact of smoking on cancer recurrence and survival in patients with stage III colon cancer: findings from intergroup trial CALGB 89803. [Abstract] J Clin Oncol 26 (Suppl 15): A-4039, 2008.

Meyerhardt JA, Niedzwiecki D, Hollis D, et al.: Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from Cancer and Leukemia Group B 89803. J Clin Oncol 26 (25): 4109-15, 2008.[PUBMED Abstract]

Meyerhardt JA, Niedzwiecki D, Hollis D, et al.: The impact of dietary patterns on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. [Abstract] J Clin Oncol 25 (Suppl 18): A-4019, 2007.

Meyerhardt JA, Niedzwiecki D, Hollis D, et al.: Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA 298 (7): 754-64, 2007.[PUBMED Abstract]

Saltz LB, Niedzwiecki D, Hollis D, et al.: Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol 25 (23): 3456-61, 2007.[PUBMED Abstract]

Meyerhardt JA, Heseltine D, Niedzwiecki D, et al.: Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol 24 (22): 3535-41, 2006.[PUBMED Abstract]

Fuchs C, Meyerhardt JA, Heseltine DL, et al.: Influence of regular aspirin use on survival for patients with stage III colon cancer: findings from Intergroup trial CALGB 89803. [Abstract] J Clin Oncol 23 (Suppl 16): A-3530, 253s, 2005.

Meyerhardt JA, Heseltine D, Niedzwiecki D, et al.: The impact of physical activity on patients with stage III colon cancer: findings from Intergroup trial CALGB 89803. [Abstract] J Clin Oncol 23 (Suppl 16): A-3534, 254s, 2005.

Saltz LB, Niedzwiecki D, Hollis D, et al.: Irinotecan plus fluorouracil/leucovorin (IFL) versus fluorouracil/leucovorin alone (FL) in stage III colon cancer (intergroup trial CALGB C89803). [Abstract] J Clin Oncol 22 (Suppl 14): A-3500, 245s, 2004.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Leonard Saltz, MD, Protocol chair		Ph: 212-639-2501; 800-525-2225

North Central Cancer Treatment Group

Richard Goldberg, MD, Protocol chair(Contact information may not be current)		Ph: 507-266-0029 Email: goldberg.richard@mayo.edu

NCIC-Clinical Trials Group

David Klaassen, MD, Protocol chair(Contact information may not be current)		Ph: 604-877-6000; 800-663-3333

Southwest Oncology Group

Alexander Hantel, MD, Protocol chair		Ph: 630-527-3788 Email: ahantel@edward.org

Eastern Cooperative Oncology Group

James Thomas, MD, PhD, Protocol chair		Ph: 614-293-8569 Email: james.thomas@osumc.edu

Registry Information
Official Title		Phase III Intergroup Trial of Irinotecan (CPT-11) (NSC# 616348) Plus Luorouracil/Leucovorin (5-FU/LV) Versus Fluorouracil/Leucovorin Alone After Curative Resection for Patients with Stage III Colon Cancer
Trial Start Date		1999-04-15
Registered in ClinicalTrials.gov		NCT00003835
Date Submitted to PDQ		1999-03-26
Information Last Verified		2008-09-10
NCI Grant/Contract Number		U10-CA31946