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

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

fluorouracil

leucovorin calcium

levamisole hydrochloride

radiation therapy

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

CCOP - Scottsdale Oncology Program
CCOP - Colorado Cancer Research Program, Inc.
H. Lee Moffitt Cancer Center and Research Institute
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Veterans Affairs Medical Center - Chicago (Lakeside)
CCOP - Evanston
CCOP - Illinois Oncology Research Association
CCOP - Carle Cancer Center
CCOP - Cedar Rapids Oncology Project
CCOP - Iowa Oncology Research Association
Siouxland Hematology-Oncology
CCOP - Ochsner
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
CCOP - Ann Arbor Regional
CCOP - Kalamazoo
CCOP - Duluth
University of Minnesota Cancer Center
CCOP - Metro-Minnesota
CCOP - Missouri Valley Cancer Consortium
Veterans Affairs Medical Center - East Orange
CCOP - Northern New Jersey
Albert Einstein Comprehensive Cancer Center
Quain & Ramstad Clinic, P.C.
CCOP - Merit Care Hospital
Altru Health Systems
Ireland Cancer Center
CCOP - Toledo Community Hospital Oncology Program
CCOP - Geisinger Clinical and Medical Center
Hahnemann University Hospital
Rapid City Regional Hospital
CCOP - Sioux Community Cancer Consortium
CCOP - Marshfield Medical Research and Education Foundation
Medical College of Wisconsin
Veterans Affairs Medical Center - Milwaukee (Zablocki)
Saskatchewan Cancer Agency
Pretoria Academic Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

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

PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FU

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

Arm 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).

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.

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.

Outcomes

Primary Outcome Measures

Survival and Relapse-free survival

Secondary Outcome Measures

Full Information

NCT ID

NCT00002551

First Posted

November 1, 1999

Last Updated

April 3, 2013

Sponsor

SWOG Cancer Research Network

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00002551

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2013

Overall Recruitment Status

Completed

Study Start Date

March 1994 (undefined)

Primary Completion Date

August 2006 (Actual)

Study Completion Date

October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

SWOG Cancer Research Network

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1917 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm 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).

Arm Title

PVI 5-FU+Pelvic XRT+PVI 5-FU+PVI 5-FU

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Other Intervention Name(s)

5-FU

Intervention Description

See arm assignments.

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Other Intervention Name(s)

leucovorin, LV

Intervention Description

See arm assignments.

Intervention Type

Drug

Intervention Name(s)

levamisole hydrochloride

Other Intervention Name(s)

LEV

Intervention Description

See arm assignments.

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Intervention Description

See arm assignments.

Primary Outcome Measure Information:

Title

Survival and Relapse-free survival

Time Frame

Until death

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials: