Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed

NCT ID: NCT00002525

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 859 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1993-10-01
• Study Completion Date: 2015-04-30

Brief 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 tumor cells. It is not yet known if surgery is more effective with or without chemotherapy for colon cancer.

PURPOSE: Randomized phase III trial to evaluate whether perioperative 5-Fluorouracil (5-FU) chemotherapy after curative resection could improve overall survival and disease-free survival in patients with Duke's B3 or C colon cancer.

Detailed Description

OBJECTIVES:

I. To determine if adjuvant therapy with one week of continuous 5-FU given within 24 hours of a curative colon resection followed by 6 months of 5-FU/leucovorin is effective in prolonging the disease-free survival and increasing overall survival in patients with Dukes' B3 or C colon cancer, when compared to patients who are treated with 5-FU/leucovorin only.

II. 1. To determine if a week of perioperative continuous 5-FU affects disease-free survival and overall survival in patients with Dukes' B2 colon cancer.

OUTLINE: This is an open-label, randomized phase III study. Patients undergo curative colon resection via laparotomy. Patients are randomized to 1 of 2 arms in a 1:1 ratio.

Arm I (Perioperative 5-FU): Within 24 hours of the colon resection, patients receive perioperative 5-fluorouracil (5-FU) intravenously (IV) over 24 hours for 7 days.

Arm II (No perioperative 5-FU): Patients receive no perioperative fluorouracil.

After surgery, patients with stage I, stage IIA, or stage IV colon cancer are immediately removed from study. Patients with stage IIB, IIC, or III colon cancer are re-registered within 35 days postoperatively. Beginning 21-35 days after surgery, patients with stage IIC or III disease receive leucovorin calcium IV bolus immediately followed by 5-FU IV bolus on days 1-5. Courses repeat every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stage IIB disease do not receive adjuvant 5-FU and leucovorin calcium.

Patients are followed every 3 months for 2 years, then every 6 months for 2 years, and then annually until 15 years.

PROJECTED ACCRUAL: A total of 800-2,000 patients (at least 400 per treatment arm) will be accrued for this study over 2-3 years.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Perioperative 5-FU

Within 24 hours of the colon resection, patients receive perioperative fluorouracil intravenously (IV) over 24 hours for 7 days.

After surgery (beginning 21-35 days post-surgery), 5-FU was given at a dose of 425 mg/m^2 IV push on days 1-5, and leucovorin calcium was given at a dose of 20mg/m^2 IV push on days 1-5

Group Type: EXPERIMENTAL

fluorouracil

Intervention Type: DRUG

Perioperative 5-FU: 600 mg/m^2/d x 7 days continuous IV, beginning within 24 hours of surgery

After surgery, 5-FU was given 425 mg/m^2 IV push on days 1-5

leucovorin calcium

Intervention Type: DRUG

given after surgery at dose of 20mg/m\^2 IV push on days 1-5

No perioperative 5-FU

Patients receive no perioperative fluorouracil.

After surgery (beginning 21-35 days post-surgery), 5-FU was given at a dose of 425 mg/m^2 IV push on days 1-5, and leucovorin calcium was given at a dose of 20mg/m^2 IV push on days 1-5

Group Type: ACTIVE_COMPARATOR

fluorouracil

Intervention Type: DRUG

Perioperative 5-FU: 600 mg/m^2/d x 7 days continuous IV, beginning within 24 hours of surgery

After surgery, 5-FU was given 425 mg/m^2 IV push on days 1-5

leucovorin calcium

Intervention Type: DRUG

given after surgery at dose of 20mg/m\^2 IV push on days 1-5

Interventions

fluorouracil

Perioperative 5-FU: 600 mg/m^2/d x 7 days continuous IV, beginning within 24 hours of surgery

After surgery, 5-FU was given 425 mg/m^2 IV push on days 1-5

Intervention Type: DRUG

leucovorin calcium

given after surgery at dose of 20mg/m\^2 IV push on days 1-5

Intervention Type: DRUG

Other Intervention Names

5-FU; Adrucil; Efudex; Leucovorin; Wellcovorin; Citrovorum factor; Folinic acid; 5-formyl tetrahydrofolate; LV; LCV

Eligibility Criteria

Inclusion Criteria

• Adenocarcinoma of the colon documented by colonoscopy or barium enema
• Tumor either considered resectable or totally resected within 24 hours prior to study
• Randomization within 2 weeks prior to surgery or within 24 hours after surgery required
• Patients randomized after surgery must meet the following criteria:

• Complete resection performed with no evidence of residual disease or distant metastases
• Distal margin of tumor above the peritoneal reflection in area of rectum
• No free perforation Intestinal obstruction allowed
• Preliminary or complementary colostomy allowed
• Concurrent registration for E3293 strongly recommended
• Age 18 and over
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate organ function based on the following tests within 2 weeks prior to randomization

• White Blood Cell (WBC) at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 2.0 mg/dL
• Creatinine no greater than 2.0 mg/dL
• No second malignancy within 5 years except: superficial non-melanomatous skin cancer and carcinoma in situ of the cervix
• Fertile patients must use adequate contraception

Exclusion Criteria

• Dual primary tumors
• Prior nonmalignant systemic disease that would preclude use of chemotherapy
• Pregnant or nursing
• Prior fluorouracil
• Other prior or concurrent chemotherapy for this malignancy
• Prior or concurrent radiotherapy for this malignancy

Eligibility Criteria for Re-registration for Patients Randomized Pre-operatively:

• Must have pathologic classification of Dukes' B2, B3, or C disease by the contributing institution.
• Must be re-registered < 35 days after surgery.
• ECOG performance status of 0-2.
• Complete resection must have been performed with no evidence of residual disease or distant metastasis.
• Distal margin of the tumor must not extend below the peritoneal reflection in the area of the rectum.
• Single primary colon carcinoma without free perforation demonstrated. Patients with intestinal obstruction are eligible. Preliminary or complementary colostomy dose not preclude entry of a patient.
• Have WBC > 3000/mm^3, platelets > 100,000/mm^3, adequate renal (serum creatinine <= 2.0mg/dL) and hepatic function (bilirubin <= 2.0mg/dL), within one week prior to beginning adjuvant chemotherapy (For Dukes' B3 and C patients only).

Eligibility Criteria for Re-registration for Patients Randomized Post-operatively:

• Must have pathologic classification of Dukes' B2, B3, or C disease by the contributing institution.
• Patient must be re-registered < 35 days after surgery.
• ECOG performance status of 0-2.
• Started perioperative 5-FU, if assigned, within 24 hours of surgery.
• Have WBC > 3000/mm^3, platelets > 100,000/mm^3, adequate renal (serum creatinine <= 2.0mg/dL) and hepatic function (bilirubin < =2.0mg/dL), within one week prior to beginning adjuvant chemotherapy (For Dukes' B3 and C patients only).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role: collaborator

American College of Surgeons

OTHER

Sponsor Role: collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role: collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary M. Kemeny, MD, FACS

Role: STUDY_CHAIR

SUNY at Stony Brook

Locations

Loyola University Medical Center

Maywood, Illinois, United States

Countries

United States

References

Kemeny M, Ibrahim J, Benson AB, et al.: Post-operative complications of continuous infusion 5 FU following curative resection of colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A923, 260a, 1997.

Reference Type: RESULT

Other Identifiers

E1292

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA023318

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000078337

Identifier Type: REGISTRY

Identifier Source: secondary_id

E1292

Identifier Type: -

Identifier Source: org_study_id