Clinical trial NCT00002525: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage II colon cancer
stage III colon cancer
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: SWOG Cancer Research Network
name: Cancer and Leukemia Group B
name: American College of Surgeons
name: NSABP Foundation Inc
First posted: 2004-04-06
Enrollment: 859
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: 5-year Overall Survival Rate in Patients With Dukes' B3/C Disease
timeFrame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Secondary outcomes:
measure: 5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease
timeFrame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
measure: 5-year Overall Survival Rate in Patients With Dukes' B2 Disease
timeFrame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
measure: 5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease
timeFrame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
affiliation: SUNY at Stony Brook
name: Mary M. Kemeny, MD, FACS
role: STUDY_CHAIR
References:
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.