Chemotherapy With or Without Isolated Hepatic Perfusion With Melphalan in Treating Patients With Colorectal Cancer That Has Spread to the Liver

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 them in different ways may kill more tumor cells. It is not yet known which chemotherapy regimen is most effective for colorectal cancer that has spread to the liver. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without isolated hepatic perfusion with melphalan in treating patients who have colorectal cancer that has spread to the liver.

Detailed Description
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OBJECTIVES: Compare the disease-free and overall survival of patients with unresectable colorectal cancer metastatic to the liver treated with regional and systemic chemotherapy with or without isolated hepatic perfusion with melphalan. Compare the response rate and duration of response in patients treated with these regimens. Compare the patterns of recurrence (liver vs systemic) in patients treated with these regimens. Compare the health-related quality of life (QOL) of patients treated with these regimens. Determine whether baseline QOL correlates with length of survival of patients treated with these regimens. OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy for liver metastasis (yes vs no) and percentage of hepatic replacement (less than 25% vs at least 25%). All patients undergo laparotomy to determine final eligibility. Eligible patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo hyperthermic isolated hepatic perfusion with melphalan over 60 minutes. Patients then undergo placement of an intrahepatic pump or port. At 6 weeks post hepatic perfusion, patients receive systemic chemotherapy comprising irinotecan IV over 90 minutes on day 1 followed by fluorouracil IV over 15 minutes and leucovorin calcium (CF) IV over 15 minutes on days 1-3. Patients receive local chemotherapy comprising floxuridine (FUDR) and CF by hepatic arterial infusion (HAI) continuously on days 14-28. Arm II: Patients undergo placement of an intrahepatic pump or port at laparotomy. At 7 days post laparotomy, patients receive FUDR and CF by HAI continuously for 14 days. Beginning 2 weeks after completion of HAI, patients receive systemic and local chemotherapy as in arm I. Treatment with combined systemic and local chemotherapy repeats every 35 days for a maximum of 6 courses. Treatment with local chemotherapy alone repeats every 28 days for a maximum of 6 additional courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, postoperatively, every third course of chemotherapy, every 3 months for 2 years, and then every 6 months thereafter. Patients are followed every 3 months for 2 years and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 168 patients (84 per treatment arm) will be accrued for this study within 54 months.

Official Title
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A Phase III Prospective Random Assignment Trial of Regional and Systemic Chemotherapy With or Without Initial Isolated Hepatic Perfusion for Patients With Metastatic Unresectable Colorectal Cancers of the Liver

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: FOLFIRI regimen
* Drug: floxuridine
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: melphalan
* Procedure: hyperthermia treatment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic colorectal cancer of the parenchyma of the liver No evidence of extrahepatic disease (limited resectable extrahepatic disease allowed) Unresectable liver metastasis, as defined by the following: More than 3 sites of disease Bilobar disease Tumor abutting major vascular or ductal structures Measurable disease No biopsy-proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices, or collateral vessels around organs drained by the portal venous system PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Platelet count greater than 100,000/mm^3 Hematocrit greater than 27.0% WBC greater than 3,000/mm^3 Hepatic: Bilirubin less than 2.0 mg/dL PT no greater than 2 seconds over upper limit of normal Elevations in transaminases secondary to metastatic disease allowed No veno-occlusive disease No active chronic hepatitis Hepatitis B or C allowed provided there is no evidence of cirrhosis Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No ischemic cardiac disease No prior congestive heart failure with LVEF less than 40% Pulmonary: No chronic obstructive pulmonary disease or other chronic pulmonary disease with pulmonary function test less than 50% of predicted Other: No active infections Not pregnant or nursing Negative pregnancy test Weight greater than 30 kg PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy for disease and recovered Chemotherapy: At least 4 weeks since prior chemotherapy for disease and recovered No prior intrahepatic artery infusion therapy with floxuridine Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy for disease and recovered Surgery: Not specified Other: No concurrent immunosuppressive drugs No concurrent chronic anticoagulants

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFIRI regimen|nan|
|Drug: floxuridine|nan|
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: leucovorin calcium|nan|
|Drug: melphalan|nan|
|Procedure: hyperthermia treatment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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