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

Postoperative Evaluation of 5-FU by Bolus Injection vs. 5-FU by Prolonged Venous Infusion Prior to and Following Combined Prolonged Venous Infusion Plus Pelvic XRT vs. Bolus 5-FU Plus Leucovorin Plus Levamisole Prior to and Following Combined Pelvic XRT Plus Bolus 5-FU Plus Leucovorin in Patients With Rectal Cancer, Phase III


Lead Sponsor: Southwest Oncology Group

Collaborator: National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Radiation Therapy Oncology Group
North Central Cancer Treatment Group
NCIC Clinical Trials Group
Cancer and Leukemia Group B

Source Southwest Oncology Group
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.

Overall Status Completed
Start Date 1994-03-01
Completion Date 2008-10-01
Primary Completion Date 2006-08-01
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Survival and Relapse-free survival Until death
Enrollment 1917

Intervention Type: Drug

Intervention Name: fluorouracil

Description: See arm assignments.

Other Name: 5-FU

Intervention Type: Drug

Intervention Name: leucovorin calcium

Description: See arm assignments.

Arm Group Label: Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV

Intervention Type: Drug

Intervention Name: levamisole hydrochloride

Description: See arm assignments.

Arm Group Label: Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV

Other Name: LEV

Intervention Type: Radiation

Intervention Name: radiation therapy

Description: See arm assignments.



DISEASE CHARACTERISTICS: Histologically proven stage II or III adenocarcinoma of the rectum Tumor extends through the bowel wall and into perirectal fat or soft tissue (TNM T3-4, N0, M0) Nodes are involved with tumor (TNM T1-4, N1-3, M0) Tumor completely resected en bloc with no gross or microscopic evidence of residual disease Circumferential (radial) margins of resected adherent tumors must be specifically documented free of disease (with the sole exception of extraperitoneal serosal margins) No evidence of metastasis No regional nodal metastases (metastases outside of the pelvis) that cannot be resected en bloc with the primary lesion No distant peritoneal metastases (metastases that are not a direct extension from the primary tumor) even if grossly resected (direct extension into another structure permitted) Abdominopelvic CT required unless: Bilirubin, SGOT, and alkaline phosphatase are within normal limits, AND Operative report describes liver as normal on exploration No tumors of colonic origin, i.e.: Lower edge of the tumor is below the peritoneal reflection or a portion of the tumor is retroperitoneally located (usually posteriorly) as defined by the surgeon at laparotomy OR Lower margin of the tumor is 12 cm or less from the anal verge by proctoscopic exam No prior history of rectal cancer No stage II or III cancers of the extrapelvic colon within the past 5 years Complete surgical resection at least 5 years prior to protocol registration allowed provided no other therapy was administered Synchronous modified stage I or IIa colorectal cancer (no nodal involvement or penetration through the muscularis propria) that has been completely resected allowed Registration between 20 and 70 days after the definitive surgical procedure required Chemotherapy must begin no later than day 70 following surgery Concurrent registration on protocol SWOG-9419 allowed for patients with adequate tissue samples PATIENT CHARACTERISTICS: Age: Over 18 Performance status: SWOG 0-2 Hematopoietic: WBC at least 4,000/mm3 Platelet count normal Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Not specified Other: No chronic ulcerative colitis No other serious medical illness that would preclude protocol therapy No psychiatric condition that would preclude informed consent No noncolorectal 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 Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics Other: No other concurrent antineoplastic therapy



Minimum Age:

18 Years

Maximum Age:


Healthy Volunteers:


Overall Official
CCOP - Scottsdale Oncology Program | Scottsdale, Arizona, 85259-5404, United States
CCOP - Colorado Cancer Research Program, Inc. | Denver, Colorado, 80209-5031, United States
H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida, 33612, United States
Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago, Illinois, 60611, United States
Veterans Affairs Medical Center - Chicago (Lakeside) | Chicago, Illinois, 60611, United States
CCOP - Evanston | Evanston, Illinois, 60201, United States
CCOP - Illinois Oncology Research Association | Peoria, Illinois, 61602, United States
CCOP - Carle Cancer Center | Urbana, Illinois, 61801, United States
CCOP - Cedar Rapids Oncology Project | Cedar Rapids, Iowa, 52403-1206, United States
CCOP - Iowa Oncology Research Association | Des Moines, Iowa, 50309-1016, United States
Siouxland Hematology-Oncology | Sioux City, Iowa, 51101-1733, United States
CCOP - Ochsner | New Orleans, Louisiana, 70121, United States
Dana-Farber Cancer Institute | Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center | Boston, Massachusetts, 02215, United States
CCOP - Ann Arbor Regional | Ann Arbor, Michigan, 48106, United States
CCOP - Kalamazoo | Kalamazoo, Michigan, 49007-3731, United States
CCOP - Duluth | Duluth, Minnesota, 55805, United States
University of Minnesota Cancer Center | Minneapolis, Minnesota, 55455, United States
CCOP - Metro-Minnesota | Saint Louis Park, Minnesota, 55416, United States
CCOP - Missouri Valley Cancer Consortium | Omaha, Nebraska, 68131, United States
Veterans Affairs Medical Center - East Orange | East Orange, New Jersey, 07018-1095, United States
CCOP - Northern New Jersey | Hackensack, New Jersey, 07601, United States
Albert Einstein Comprehensive Cancer Center | Bronx, New York, 10461, United States
Quain & Ramstad Clinic, P.C. | Bismarck, North Dakota, 58501, United States
CCOP - Merit Care Hospital | Fargo, North Dakota, 58122, United States
Altru Health Systems | Grand Forks, North Dakota, 58201, United States
Ireland Cancer Center | Cleveland, Ohio, 44106-5065, United States
CCOP - Toledo Community Hospital Oncology Program | Toledo, Ohio, 43623-3456, United States
CCOP - Geisinger Clinical and Medical Center | Danville, Pennsylvania, 17822-2001, United States
Hahnemann University Hospital | Philadelphia, Pennsylvania, 19102-1192, United States
Rapid City Regional Hospital | Rapid City, South Dakota, 57709, United States
CCOP - Sioux Community Cancer Consortium | Sioux Falls, South Dakota, 57105-1080, United States
CCOP - Marshfield Medical Research and Education Foundation | Marshfield, Wisconsin, 54449, United States
Medical College of Wisconsin | Milwaukee, Wisconsin, 53226, United States
Veterans Affairs Medical Center - Milwaukee (Zablocki) | Milwaukee, Wisconsin, 53295, United States
Saskatchewan Cancer Agency | Regina, Saskatchewan, S4S 6X3, Canada
Pretoria Academic Hospital | Pretoria, 0001, South Africa
Location Countries


South Africa

United States

Verification Date


Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Bolus 5-FU, Pelvic XRT + PVI 5-FU, Bolus 5-FU

Type: Experimental

Description: Bolus 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).

Label: PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FU

Type: Experimental

Description: 5-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.

Label: Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV

Type: Experimental

Description: 5-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.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News