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

April 3, 2013 updated by: Southwest Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1917

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bolus 5-FU, Pelvic XRT + PVI 5-FU, Bolus 5-FU
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).
Drug: fluorouracil
See arm assignments.
Other Names:
  • 5-FU
Radiation: radiation therapy
See arm assignments.
Experimental: PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FU
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.
Drug: fluorouracil
See arm assignments.
Other Names:
  • 5-FU
Radiation: radiation therapy
See arm assignments.
Experimental: Bol 5-FU+LV+LEV+Pel XRT+Bol 5-FU+LV Bol 5-FU + LV + LEV
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.
Drug: fluorouracil
See arm assignments.
Other Names:
  • 5-FU
Radiation: radiation therapy
See arm assignments.
Drug: leucovorin calcium
See arm assignments.
Other Names:
  • LV
  • leucovorin
Drug: levamisole hydrochloride
See arm assignments.
Other Names:
  • LEV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival and Relapse-free survival
Time Frame: Until death
Until death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

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

Investigators

  • Study Chair: Robert J. Mayer, MD, FACP, Dana-Farber Cancer Institute
  • Study Chair: Stephen R. Smalley, MD, University of Kansas
  • Study Chair: Michael J. O'Connell, MD, Mayo Clinic
  • Study Chair: Anthony LA Fields, MD, FRCPC, Cross Cancer Institute at University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1994

Primary Completion (Actual)

August 1, 2006

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

June 9, 2004

First Posted (Estimate)

June 10, 2004

Study Record Updates

Last Update Posted (Estimate)

April 5, 2013

Last Update Submitted That Met QC Criteria

April 3, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000063349
  • U10CA032102 (U.S. NIH Grant/Contract)
  • SWOG-9304 (Other Identifier: SWOG)
  • CAN-NCIC-CO11 (Other Identifier: NCIC)
  • NCCTG-934751 (Other Identifier: NCCTG)
  • RTOG-9403 (Other Identifier: RTOG)
  • CLB-C9491 (Other Identifier: CALGB)
  • INT-0144 (Other Identifier: CTEP)

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 register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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