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SWOG-9304 Chemotherapy Plus Radiation Therapy in Treating Patients With Rectal Cancer That Has Been Surgically Removed

Phase 3
Completed
Conditions
Colorectal Cancer
Interventions
Registration Number
NCT00002551
Lead Sponsor
SWOG Cancer Research Network
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which treatment regimen is more effective for rectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus radiation therapy in treating patients who have rectal cancer that has been surgically removed.

Detailed Description

OBJECTIVES: I. Compare the overall and relapse free survival of patients with stage II or III rectal cancer treated with one of the following three regimens: bolus injections of fluorouracil (5-FU) prior to and following pelvic irradiation plus protracted venous infusion (PVI) 5-FU radiosensitization vs PVI 5-FU prior to and following pelvic irradiation plus PVI 5-FU radiosensitization vs bolus 5-FU with leucovorin calcium and levamisole prior to and following pelvic irradiation. II. Describe relapse patterns and tolerance associated with these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of prior surgery (abdominoperineal resection vs anterior resection), nodal status (N0 vs N1 vs N2-3), depth of tumor invasion (T1-2 vs T3 vs T4a vs T4b), time from surgery to study entry (20-45 days vs 46-70 days), participating center, and performance status (0-1 vs 2). Patients are randomized to one of three treatment arms. Arm I: Patients receive fluorouracil (5-FU) IV on days 1-5 and 29-33. 5-FU is then given as a continuous infusion beginning on day 57 and continuing concurrently with radiotherapy for 5 weeks. Following a 28 day break from treatment patients receive 5-FU IV on days 1-5 of a 28 day course. Postradiotherapy treatment repeats for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive 5-FU IV continuously on days 1-42. 5-FU and radiotherapy are then administered as in arm II. Arm III: Patients receive leucovorin calcium (CF) IV followed by 5-FU IV on days 1-5 and 29-33. Patients also receive oral levamisole twice daily on days 1-3, 15-17, 29-31, and 43-45. CF IV and 5-FU IV are then given on days 57-60 and 85-88 concurrently with radiotherapy. Following a 28 day break from treatment patients receive CF IV and 5-FU IV on days 1-5 and 29-33 and oral levamisole twice daily on days 1-3, 15-17, 29-31, and 43-45 in the absence of disease progression or unacceptable toxicity. All patients receive radiotherapy 5 days per week for 5 weeks starting on day 57. Patients are followed every 4 months for 2 years, then every 6 months for 4 years, and then annually until death.

PROJECTED ACCRUAL: A total of 1,800 patients (600 per arm) will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1917
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEVleucovorin calcium5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
Bolus 5-FU, Pelvic XRT + PVI 5-FU, Bolus 5-FUfluorouracilBolus 5-FU (fluorouracil) (500mg/m2/day on days 1-5, 29-33), Pelvic XRT + PVI 5-FU, Bolus 5-FU (450mg/m2/day for 5 days beginning 28 days after RT, for 2 cycles on days 1-5 of a 28 days cycle).
Bolus 5-FU, Pelvic XRT + PVI 5-FU, Bolus 5-FUradiation therapyBolus 5-FU (fluorouracil) (500mg/m2/day on days 1-5, 29-33), Pelvic XRT + PVI 5-FU, Bolus 5-FU (450mg/m2/day for 5 days beginning 28 days after RT, for 2 cycles on days 1-5 of a 28 days cycle).
PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FUfluorouracil5-FU (fluorouracil) 300mg/m2/day for 42 days followed by 2 week interruption, Day 57 through XRT will receive 225mg/m2/day of 5-FU followed by 1 month interruption, 4 weeks after completion of XRT 1 8wk cycle of 5-FU 300mg/m2/day.
PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FUradiation therapy5-FU (fluorouracil) 300mg/m2/day for 42 days followed by 2 week interruption, Day 57 through XRT will receive 225mg/m2/day of 5-FU followed by 1 month interruption, 4 weeks after completion of XRT 1 8wk cycle of 5-FU 300mg/m2/day.
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEVlevamisole hydrochloride5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEVradiation therapy5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEVfluorouracil5-FU (fluorouracil) 425/mg/m2/day Days 1-5,29-33; LV (leucovorin calcium) 20mg/m2/day Days 1-5,29-33; LEV (levamisole hydrochloride) 150mg/day (50mg TID) for 3 days every 14 days starting after each course of 5-FU. During RT: 5-FU and LV 4 days on wk 1 and wk 5 of RT. LV 20 mg/m2/day IV bolus within 2hrs after completion of that day's radiation therapy, for four days in each cycle. Followed immediately by 5- FU 400 mg/m2/day IV bolus. Treatment will be given on days 57 - 60 and 85 - 88.Treatment post-RT-chemotherapy 28 days after completion of RT consist of 5 days of chemotherapy in 28 day cycles. 5-FU, 380 mg/m2/day on days 1 - 5 and LV given at a dose of 20 mg/m2/day on days 1 - 5 with the 5-FU given immediately after the LV. For 2 post-radiation cycles on days 1 - 5 of a 28 day cycle. Levamisole will be given orally at a dose of 150 mg/day (50 mg tid) for 3 days every 14 days during the 1st 3 days of each cycle of 5-FU, and again 14 days after starting each course of 5-FU.
Primary Outcome Measures
NameTimeMethod
Survival and Relapse-free survivalUntil death
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (37)

CCOP - Marshfield Medical Research and Education Foundation

🇺🇸

Marshfield, Wisconsin, United States

Hahnemann University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

🇺🇸

Chicago, Illinois, United States

Veterans Affairs Medical Center - Chicago (Lakeside)

🇺🇸

Chicago, Illinois, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Ireland Cancer Center

🇺🇸

Cleveland, Ohio, United States

CCOP - Evanston

🇺🇸

Evanston, Illinois, United States

CCOP - Colorado Cancer Research Program, Inc.

🇺🇸

Denver, Colorado, United States

University of Minnesota Cancer Center

🇺🇸

Minneapolis, Minnesota, United States

CCOP - Scottsdale Oncology Program

🇺🇸

Scottsdale, Arizona, United States

CCOP - Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

🇺🇸

Cedar Rapids, Iowa, United States

CCOP - Illinois Oncology Research Association

🇺🇸

Peoria, Illinois, United States

CCOP - Iowa Oncology Research Association

🇺🇸

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

🇺🇸

Sioux City, Iowa, United States

CCOP - Duluth

🇺🇸

Duluth, Minnesota, United States

CCOP - Metro-Minnesota

🇺🇸

Saint Louis Park, Minnesota, United States

CCOP - Kalamazoo

🇺🇸

Kalamazoo, Michigan, United States

Veterans Affairs Medical Center - East Orange

🇺🇸

East Orange, New Jersey, United States

CCOP - Northern New Jersey

🇺🇸

Hackensack, New Jersey, United States

Albert Einstein Comprehensive Cancer Center

🇺🇸

Bronx, New York, United States

Altru Health Systems

🇺🇸

Grand Forks, North Dakota, United States

Quain & Ramstad Clinic, P.C.

🇺🇸

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

🇺🇸

Fargo, North Dakota, United States

CCOP - Toledo Community Hospital Oncology Program

🇺🇸

Toledo, Ohio, United States

CCOP - Geisinger Clinical and Medical Center

🇺🇸

Danville, Pennsylvania, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

🇺🇸

Sioux Falls, South Dakota, United States

Saskatchewan Cancer Agency

🇨🇦

Regina, Saskatchewan, Canada

Pretoria Academic Hospital

🇿🇦

Pretoria, South Africa

H. Lee Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

CCOP - Missouri Valley Cancer Consortium

🇺🇸

Omaha, Nebraska, United States

Veterans Affairs Medical Center - Milwaukee (Zablocki)

🇺🇸

Milwaukee, Wisconsin, United States

CCOP - Ann Arbor Regional

🇺🇸

Ann Arbor, Michigan, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

CCOP - Ochsner

🇺🇸

New Orleans, Louisiana, United States

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