S9415 Chemotherapy in Patients With Stage II or III Colon Cancer That Has Been Surgically Removed

Study Overview
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Brief Summary
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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 cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given in different ways in treating patients with surgically removed stage II or stage III colon cancer at high risk of recurrence.

Detailed Description
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OBJECTIVES: I. Compare overall and disease free survival in patients with completely resected stage II or III colon cancer randomized to adjuvant chemotherapy with bolus fluorouracil and leucovorin calcium with levamisole vs continuous infusion fluorouracil with levamisole. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, T stage (T1 vs T2 vs T3 vs T4a), N stage (N0 vs N1 vs N2-3), and time from surgery until registration (21-28 vs 29-35 days). Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV immediately followed by fluorouracil IV on days 1 through 5 of weeks 1, 5, 9, 14, 19, and 24, and oral levamisole 3 times a day for 3 days on days 1-3. Courses repeat every 2 weeks for 6 months. Arm II: Patients receive levamisole as in arm I plus fluorouracil by continuous IV infusion for 8 weeks. Treatment with fluorouracil repeats every 10 weeks for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 9 months and 12 months, then every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for the study over approximately 5.5 years.

Official Title
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Phase III Randomized Trial of 5-FU/Leucovorin/Levamisole Versus 5-FU Continuous Infusion/Levamisole as Adjuvant Therapy for High-Risk Resectable Colon Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: levamisole hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven resectable stage II or III adenocarcinoma of the colon Caudal margin of the primary tumor must lie above the peritoneal reflection Must have pathologic confirmation of either N1-3 (stage III), or if N0, must have T3-T4 (stage II) with bowel obstruction or perforation Obstruction documented as: At least 75% colon or small bowel obstruction on x-ray and/or endoscopy Significant bowel dilatation surgically documented Significant obstruction described in the pathology report Perforation documented by gross operative/pathologic evidence of a colon wall defect with associated abscess or peritonitis Complete en bloc resection by laparotomy required No laparoscopic colectomy without prior surgery on protocol SWOG-9411 No gross or microscopic residual disease No distant peritoneal metastases (stage IV) even if grossly resectable No requirement to open the pelvic peritoneum to define the extent of disease No extrapelvic nodal metastasis unless resected en bloc with the primary tumor No distant metastases No other diagnosis of stage II-III colon cancer within the past 5 years May have undergone complete surgical resection at least 5 years prior to study Completely resected prior or synchronous stage 0-I colon cancer eligible PATIENT CHARACTERISTICS: Age: Adult Performance status: SWOG 0-2 Hematopoietic: WBC (white blood cell) at least 3,500/mm3 Platelet count at least within the lower limit of normal Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST (angiotensin sensitivity test) no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Creatinine no greater than 2 times ULN Other: No organic brain syndrome, Alzheimer's disease, or other altered mental status No second malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer Adequately treated carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Effective contraception required of fertile patients PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior fluorouracil or other chemotherapy for cancer No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior or concurrent radiotherapy for cancer Surgery: Complete en bloc resection required (see Disease Characteristics)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5-FU/Leucovorin/Levamisole<br>levamisole hydrochloride: 50 mg every 8 hours x 3 days, PO, repeat every 14 days for 6 months; leucovorin calcium: 20 mg/m^2/day, IV, Days 1-5 of each cycle; 5-fluorouracil: 425 mg/m^2/day, IV, Days 1-5 of each cycle; | Drug: fluorouracil<br>* Given IV as described in Arm Description<br>* Other names: NSC-19893;Drug: leucovorin calcium<br>* Given IV as described in Arm description.<br>* Other names: NSC-3590;Drug: levamisole hydrochloride<br>* Given as described in arm description<br>* Other names: NSC-177023;|
| Active Comparator: Infusional 5-FU + Levamisole<br>levamisole hydrochloride : 50 mg every 8 hours x 3 days, PO, repeat every 14 days for 6 months; 5-fluorouracil: 250 mg/m^2/day, continuous infusion, daily for 56 days x 3 cycles of 8 weeks. | Drug: fluorouracil<br>* Given IV as described in Arm Description<br>* Other names: NSC-19893;Drug: levamisole hydrochloride<br>* Given as described in arm description<br>* Other names: NSC-177023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare effectiveness of bolus 5-FU, leucovorin, levamisole vs continuous infusion 5-FU, levamisole as adjuvant therapy for patients with colon cancer, measured in overall survival |  | At death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | Until progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II colon cancer, stage III colon cancer