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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002525
Recruitment Status : Terminated (The study was stopped before reaching its accrual goal due to slow accrual)
First Posted : April 6, 2004
Results First Posted : July 20, 2016
Last Update Posted : August 29, 2016
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 )

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE April 6, 2004
Results First Submitted Date  ICMJE April 8, 2016
Results First Posted Date  ICMJE July 20, 2016
Last Update Posted Date August 29, 2016
Study Start Date  ICMJE August 1993
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2016)
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 ]
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
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00002525 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2016)
  • 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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed
Official Title  ICMJE Phase III Intergroup Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection, Followed by 5-FU/Leucovorin for Patients With Colon Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: fluorouracil
    • Drug: leucovorin calcium
  • 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

    Interventions:
    • Drug: fluorouracil
    • Drug: leucovorin calcium
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 8, 2016)
859
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00002525
Other Study ID Numbers  ICMJE E1292
E1292 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
U10CA023318 ( U.S. NIH Grant/Contract )
CDR0000078337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Responsible Party Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
Study Sponsor  ICMJE ECOG-ACRIN Cancer Research Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Southwest Oncology Group
  • Cancer and Leukemia Group B
  • American College of Surgeons
  • NSABP Foundation Inc
Investigators  ICMJE
Study Chair: Mary M. Kemeny, MD, FACS SUNY at Stony Brook
PRS Account Eastern Cooperative Oncology Group
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP