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

This study has been terminated.
(The study was stopped before reaching its accrual goal due to slow accrual)
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Southwest Oncology Group
Cancer and Leukemia Group B
American College of Surgeons
NSABP Foundation Inc
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT00002525
First received: November 1, 1999
Last updated: July 19, 2016
Last verified: July 2016
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: fluorouracil
Drug: leucovorin calcium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Intergroup Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection, Followed by 5-FU/Leucovorin for Patients With Colon Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 5-year Overall Survival Rate in Patients With Dukes' B3/C Disease [ Time Frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. Kaplan-Meier method was used to estimate 5-year OS rate


Secondary Outcome Measures:
  • 5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease [ Time Frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer, or deaths, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Patients without any follow up data were censored at random assignment. Kaplan-Meier method was used to estimate the 5-year DFS rate.

  • 5-year Overall Survival Rate in Patients With Dukes' B2 Disease [ Time Frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. Kaplan-Meier method was used to estimate 5-year OS rate

  • 5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease [ Time Frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer, or deaths, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Patients without any follow up data were censored at random assignment. Kaplan-Meier method was used to estimate the 5-year DFS rate.


Enrollment: 859
Study Start Date: August 1993
Study Completion Date: April 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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

Drug: 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

Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: leucovorin calcium
given after surgery at dose of 20mg/m^2 IV push on days 1-5
Other Names:
  • Leucovorin
  • Wellcovorin
  • Citrovorum factor
  • Folinic acid
  • 5-formyl tetrahydrofolate
  • LV
  • LCV
Active Comparator: 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

Drug: 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

Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: leucovorin calcium
given after surgery at dose of 20mg/m^2 IV push on days 1-5
Other Names:
  • Leucovorin
  • Wellcovorin
  • Citrovorum factor
  • Folinic acid
  • 5-formyl tetrahydrofolate
  • LV
  • LCV

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria for Randomization:

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002525

Locations
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Southwest Oncology Group
Cancer and Leukemia Group B
American College of Surgeons
NSABP Foundation Inc
Investigators
Study Chair: Mary M. Kemeny, MD, FACS SUNY at Stony Brook
  More Information

Publications:
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.

Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT00002525     History of Changes
Other Study ID Numbers: E1292  E1292  U10CA023318  CDR0000078337 
Study First Received: November 1, 1999
Results First Received: April 8, 2016
Last Updated: July 19, 2016
Health Authority: United States: Federal Government
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Keywords provided by Eastern Cooperative Oncology Group:
stage II colon cancer
stage III colon cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Calcium, Dietary
Fluorouracil
Levoleucovorin
Leucovorin
Formyltetrahydrofolates
Tetrahydrofolates
Bone Density Conservation Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on December 07, 2016