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

Primary Purpose

Colorectal Cancer

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
fluorouracil
leucovorin calcium
Sponsored by
ECOG-ACRIN Cancer Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage II colon cancer, stage III colon cancer

Eligibility Criteria

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

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).

Sites / Locations

  • Loyola University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Perioperative 5-FU

No perioperative 5-FU

Arm Description

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

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

Outcomes

Primary Outcome Measures

5-year Overall Survival Rate in Patients With Dukes' B3/C Disease
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
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
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
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.

Full Information

First Posted
November 1, 1999
Last Updated
June 13, 2023
Sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI), SWOG Cancer Research Network, Cancer and Leukemia Group B, American College of Surgeons, NSABP Foundation Inc
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1. Study Identification

Unique Protocol Identification Number
NCT00002525
Brief Title
Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
The study was stopped before reaching its accrual goal due to slow accrual
Study Start Date
October 1, 1993 (Actual)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI), SWOG Cancer Research Network, Cancer and Leukemia Group B, American College of Surgeons, NSABP Foundation Inc

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage II colon cancer, stage III colon cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
859 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Perioperative 5-FU
Arm Type
Experimental
Arm Description
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
Arm Title
No perioperative 5-FU
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-FU, Adrucil, Efudex
Intervention Description
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
Intervention Name(s)
leucovorin calcium
Other Intervention Name(s)
Leucovorin, Wellcovorin, Citrovorum factor, Folinic acid, 5-formyl tetrahydrofolate, LV, LCV
Intervention Description
given after surgery at dose of 20mg/m^2 IV push on days 1-5
Primary Outcome Measure Information:
Title
5-year Overall Survival Rate in Patients With Dukes' B3/C Disease
Description
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
Time Frame
every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Secondary Outcome Measure Information:
Title
5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease
Description
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.
Time Frame
every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Title
5-year Overall Survival Rate in Patients With Dukes' B2 Disease
Description
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
Time Frame
every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Title
5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease
Description
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.
Time Frame
every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary M. Kemeny, MD, FACS
Organizational Affiliation
SUNY at Stony Brook
Official's Role
Study Chair
Facility Information:
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Citations:
Citation
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.
Results Reference
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Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed

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