S9415 Chemotherapy in Patients With Stage II or III Colon Cancer That Has Been Surgically Removed

Colorectal Cancer Clinical Trial

Official title:

Phase III Randomized Trial of 5-FU/Leucovorin/Levamisole Versus 5-FU Continuous Infusion/Levamisole as Adjuvant Therapy for High-Risk Resectable Colon Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002593
• Other study ID #: CDR0000063773
• Secondary ID: SWOG-9415CLB-949
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: January 2, 2013
• Start date: December 1994
• Est. completion date: March 2005

Study information

• Verified date: January 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given in different ways in treating patients with surgically removed stage II or stage III colon cancer at high risk of recurrence.

Description:

OBJECTIVES: I. Compare overall and disease free survival in patients with completely resected stage II or III colon cancer randomized to adjuvant chemotherapy with bolus fluorouracil and leucovorin calcium with levamisole vs continuous infusion fluorouracil with levamisole.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, T stage (T1 vs T2 vs T3 vs T4a), N stage (N0 vs N1 vs N2-3), and time from surgery until registration (21-28 vs 29-35 days). Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV immediately followed by fluorouracil IV on days 1 through 5 of weeks 1, 5, 9, 14, 19, and 24, and oral levamisole 3 times a day for 3 days on days 1-3. Courses repeat every 2 weeks for 6 months. Arm II: Patients receive levamisole as in arm I plus fluorouracil by continuous IV infusion for 8 weeks. Treatment with fluorouracil repeats every 10 weeks for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 9 months and 12 months, then every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for the study over approximately 5.5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1135
• Est. completion date: March 2005
• Est. primary completion date: December 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS: Histologically proven resectable stage II or III adenocarcinoma of the colon Caudal margin of the primary tumor must lie above the peritoneal reflection Must have pathologic confirmation of either N1-3 (stage III), or if N0, must have T3-T4 (stage II) with bowel obstruction or perforation Obstruction documented as: At least 75% colon or small bowel obstruction on x-ray and/or endoscopy Significant bowel dilatation surgically documented Significant obstruction described in the pathology report Perforation documented by gross operative/pathologic evidence of a colon wall defect with associated abscess or peritonitis Complete en bloc resection by laparotomy required No laparoscopic colectomy without prior surgery on protocol SWOG-9411 No gross or microscopic residual disease No distant peritoneal metastases (stage IV) even if grossly resectable No requirement to open the pelvic peritoneum to define the extent of disease No extrapelvic nodal metastasis unless resected en bloc with the primary tumor No distant metastases No other diagnosis of stage II-III colon cancer within the past 5 years May have undergone complete surgical resection at least 5 years prior to study Completely resected prior or synchronous stage 0-I colon cancer eligible

PATIENT CHARACTERISTICS: Age: Adult Performance status: SWOG 0-2 Hematopoietic: WBC (white blood cell) at least 3,500/mm3 Platelet count at least within the lower limit of normal Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST (angiotensin sensitivity test) no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Creatinine no greater than 2 times ULN Other: No organic brain syndrome, Alzheimer's disease, or other altered mental status No second malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer Adequately treated carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior fluorouracil or other chemotherapy for cancer No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior or concurrent radiotherapy for cancer Surgery: Complete en bloc resection required (see Disease Characteristics)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• fluorouracil
Given IV as described in Arm Description
• leucovorin calcium
Given IV as described in Arm description.
• levamisole hydrochloride
Given as described in arm description

Locations

Country	Name	City	State
Canada	Saskatchewan Cancer Agency	Regina	Saskatchewan
Puerto Rico	Veterans Affairs Medical Center - San Juan	San Juan
South Africa	Pretoria Academic Hospital	Pretoria
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Quain & Ramstad Clinic, P.C.	Bismarck	North Dakota
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Lakeside)	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Geisinger Clinical and Medical Center	Danville	Pennsylvania
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	Altru Health Systems	Grand Forks	North Dakota
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Mount Sinai Medical Center, NY	New York	New York
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of Rochester Cancer Center	Rochester	New York
United States	CentraCare Clinic	Saint Cloud	Minnesota
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	Stanford University Medical Center	Stanford	California
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Southwest Oncology Group	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, National Cancer Institute (NCI), North Central Cancer Treatment Group

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico,  South Africa, 

References & Publications (4)

Leichman CG, Poplin E, Zalupski M, et al.: A pilot trial of infusion 5-fluorouracil with levamisole as adjuvant therapy for stage III colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-460, 196, 1995.

Poplin E, Benedetti J, Estes N, et al.: Phase III randomized trial of bolus 5-FU/leucovorin/levamisole versus 5-FU continuous infusion/levamisole as adjuvant therapy for high risk colon cancer (SWOG 9415/INT-0153). [Abstract] Proceedings of the American S

Poplin EA, Benedetti JK, Estes NC, Haller DG, Mayer RJ, Goldberg RM, Weiss GR, Rivkin SE, Macdonald JS. Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous inf — View Citation

Yothers G, Sargent DJ, Wolmark N, Goldberg RM, O'Connell MJ, Benedetti JK, Saltz LB, Dignam JJ, Blackstock AW; ACCENT Collaborative Group. Outcomes among black patients with stage II and III colon cancer receiving chemotherapy: an analysis of ACCENT adjuvant trials. J Natl Cancer Inst. 2011 Oct 19;103(20):1498-506. doi: 10.1093/jnci/djr310. Epub 2011 Oct 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare effectiveness of bolus 5-FU, leucovorin, levamisole vs continuous infusion 5-FU, levamisole as adjuvant therapy for patients with colon cancer, measured in overall survival		At death	No
Secondary	Disease free survival		Until progression	No