Hepatic Arterial Infusion With Floxuridine and Systemic Irinotecan After Surgery in Treating Patients With Hepatic (Liver) Metastases From Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as floxuridine and irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Combining more than one drug and giving them in different ways may kill any tumor cells remaining after surgery. PURPOSE: Phase II trial to study the effectiveness of systemic irinotecan and hepatic arterial infusion with floxuridine after surgery in treating patients who have hepatic (liver) metastases from colorectal cancer.

Detailed Description
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OBJECTIVES: Determine the toxicity of hepatic arterial infusion with floxuridine and systemic irinotecan adjuvant to liver metastases resection or ablation with or without resection in patients with hepatic metastases secondary to colorectal cancer. Determine the overall survival of patients treated with this regimen. Determine the time to any hepatic recurrence or progression in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to prior therapy (liver metastases resection only vs ablation with or without resection). Within 4-8 weeks after prior resection or ablation, patients receive hepatic arterial infusion of floxuridine continuously on days 1-14 and irinotecan IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of unacceptable toxicity. Patients are followed every 3 months for 2 years.

Official Title
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A Phase II Trial Of Toxicity Assessment In Two Cohorts Of Patients (Resection Alone Or Ablation With Or Without Resection Of Hepatic Metastases From Colorectal Cancer) Treated With Adjuvant Hepatic Arterial Infusion (HAI) FUDR Plus Systemic CPT-11

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: floxuridine
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic colorectal adenocarcinoma Primary colorectal adenocarcinoma that has been completely resected (R0 disease) No evidence of residual, viable tumor by abdominal/pelvic helical CT scan or MRI with IV contrast Metastatic disease No more than 9 liver metastases All lesions completely resected or completely treated by ablation (with or without resection) All lesions treated by ablation must have been less than 5 cm in size and at least 5 mm away from main/left/right portal vein, common bile duct, and inferior vena cava All resected lesions must have a negative surgical margin (R0) Disease progression after prior systemic irinotecan for metastatic disease allowed No extrahepatic metastases confirmed by chest CT scan except colorectal mesenteric lymph node metastases resected at the time of primary tumor resection No other prior resection of extrahepatic metastases Must have the entire liver remnant perfused with a single catheter Must have a nuclear medicine macro-aggregated albumin flow scan to confirm the area of pump perfusion before study registration PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Zubrod 0-2 Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Absolute granulocyte count at least 1,500/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 2 mg/dL Alkaline phosphatase no greater than 2.0 times upper limit of normal (ULN) AST and ALT no greater than 2.0 times ULN No active hepatitis B or C infection No histological evidence of cirrhosis Renal Creatinine no greater than 1.5 times ULN Calcium less than 1.3 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Postmenopausal women must be amenorrheic for at least 12 consecutive months to be deemed not fertile Medically fit to begin chemotherapy between 4 and 8 weeks after surgery Prior cancer allowed if all of the following criteria are met: Undergone potentially curative therapy for all prior malignancies No other malignancy within the past 5 years except the following: Effectively treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix that has been effectively treated by surgery alone Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by surgery alone No evidence of recurrence of any prior malignancy No prior hepatic arterial infusion pump malfunction, malperfusion, or infection PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunologic or biologic therapy Chemotherapy No prior chemotherapy within 4 weeks before hepatic resection or hepatic ablation (with or without resection) No prior hepatic arterial infusion with fluorouracil or floxuridine Radiotherapy No concurrent adjuvant radiotherapy to the pelvis No other concurrent radiotherapy Other No other concurrent systemic therapy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: floxuridine + irinotecan<br>Within 4-8 weeks after prior resection or ablation, patients receive hepatic arterial infusion of floxuridine continuously on days 1-14 and irinotecan IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of unacceptable toxicity. Patients are followed every 3 months for 2 years. | Drug: floxuridine<br> <br> Drug: irinotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to hepatic recurrence or progression |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, stage IV rectal cancer, liver metastases