Combination Chemotherapy in Treating Patients With Stage III Colon Cancer

Study Overview
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Brief Summary
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Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for stage III colon cancer. Randomized phase III trial to compare the effectiveness of fluorouracil plus leucovorin with or without irinotecan in treating patients who have undergone surgery for stage III colon cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Compare the overall and disease free survival of patients with stage III colon cancer treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan. II. Assess prognostic markers and correlate their expression with disease free and overall survival of these patients. III. Assess the influence of diet, body mass index, and physical activity on the risk of cancer recurrence and survival in these patients. IV. Assess the influence of diet, obesity, and physical activity on the risk of toxicity associated with adjuvant therapy in these patients. V. Determine whether pathological features (including tumor grade, tumor mitotic (proliferation) index, tumor border configuration, and host lymphoid response to tumor; and lymphatic vessel, venous vessel and perineural invasion) predict outcome in this patient population. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node involvement (1-3 vs 4 or more), histology (poorly differentiated or undifferentiated vs well or moderately differentiated), and preoperative serum CEA (less than 5.0 ng/mL vs at least 5.0 ng/mL vs unknown). Study therapy must begin within 21-56 days after surgery. Patients are randomized to one of two treatment arms: ARM I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV beginning 1 hour into leucovorin calcium infusion weekly for 6 weeks. Treatment is repeated every 8 weeks for 4 courses. ARM II: Patients receive irinotecan IV over 90 minutes, followed by leucovorin calcium IV, then followed by fluorouracil IV weekly for 4 weeks. Treatment is repeated every 6 weeks for 5 courses. Patients complete a food questionnaire at the beginning of the third course and then at 6 months after study therapy. Patients are followed every 3 months for 2 years, every 4 months for 2 years, then annually thereafter. PROJECTED ACCRUAL: A total of 1260 patients will be accrued for this study within 3 years.

Official Title
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Phase III Intergroup Trial of Irinotecan (CPT-11) (NSC# 616348) Plus Fluorouracil/Leucovorin (5-FU/LV) Versus Fluorouracil/Leucovorin Alone After Curative Resection for Patients With Stage III Colon Cancer

Conditions
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Adenocarcinoma of the Colon, Stage III Colon Cancer

Intervention / Treatment
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* Drug: leucovorin calcium
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection; tumor must have been completely resected, including negative radial resecting margins There must be no history of distant metastatic disease at the time of registration Pathological evaluation must show Modified Astler-Coller stage C (TxN1-2M0) disease No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years Zubrod performance status of 0-2 Non-pregnant and not nursing, as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study Granulocytes >= 1,500/ul Platelet count >= 100,000/ul Creatinine =< 1.5 x upper limits of normal Bilirubin =< upper limit of normal

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 |
| --- | --- |
| Experimental: Arm I (leucovorin calcium and fluorouracil)<br>Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV beginning 1 hour into leucovorin calcium infusion weekly for 6 weeks. Treatment is repeated every 8 weeks for 4 courses. | Drug: leucovorin calcium<br>* Given IV<br>Drug: fluorouracil<br>* Given IV<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II (leucovorin calcium, fluorouracil, irinotrcan)<br>Patients receive irinotecan IV over 90 minutes, followed by leucovorin calcium IV, then followed by fluorouracil IV weekly for 4 weeks. Treatment is repeated every 6 weeks for 5 courses | Drug: leucovorin calcium<br>* Given IV<br>Drug: fluorouracil<br>* Given IV<br>Drug: irinotecan hydrochloride<br>* Given IV<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrence | The Cox proportional hazards model will be used to determine the association between each marker and time to recurrence and survival controlling for other baseline factors such as age, gender, treatment, primary tumor site, degree of differentiation. | From time of resection until documented disease progression, assessed up to 6 years | 
| Survival | The Cox proportional hazards model will be used to determine the association between each marker and time to recurrence and survival controlling for other baseline factors such as age, gender, treatment, primary tumor site, degree of differentiation. | Up to 6 years |