Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed
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| ClinicalTrials.gov Identifier: NCT00002525 |
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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
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Colorectal Cancer | Drug: fluorouracil Drug: leucovorin calcium | Phase 3 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 859 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | August 1993 |
| Actual Primary Completion Date : | February 2015 |
| Actual Study Completion Date : | April 2015 |
| Arm | Intervention/treatment |
|---|---|
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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:
Drug: leucovorin calcium given after surgery at dose of 20mg/m^2 IV push on days 1-5
Other Names:
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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:
Drug: leucovorin calcium given after surgery at dose of 20mg/m^2 IV push on days 1-5
Other Names:
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- 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
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
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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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002525
| United States, Illinois | |
| Loyola University Medical Center | |
| Maywood, Illinois, United States, 60153 | |
| Study Chair: | Mary M. Kemeny, MD, FACS | SUNY at Stony Brook |
| Responsible Party: | ECOG-ACRIN Cancer Research Group |
| ClinicalTrials.gov Identifier: | NCT00002525 |
| Other Study ID Numbers: |
E1292 E1292 ( Other Identifier: ECOG-ACRIN Cancer Research Group ) U10CA023318 ( U.S. NIH Grant/Contract ) CDR0000078337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) |
| First Posted: | April 6, 2004 Key Record Dates |
| Results First Posted: | July 20, 2016 |
| Last Update Posted: | August 29, 2016 |
| Last Verified: | July 2016 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy. |
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stage II colon cancer stage III colon cancer |
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Colonic Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Leucovorin Tetrahydrofolates Formyltetrahydrofolates Fluorouracil |
Calcium Levoleucovorin Calcium-Regulating Hormones and 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 Micronutrients |