Intravenous or Hepatic Arterial Infusion of Fotemustine in Treating Patients With Unresectable Liver Metastases From Eye Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fotemustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different ways may kill more tumor cells. It is not yet known whether giving fotemustine as an intravenous infusion is more effective than giving it as a hepatic arterial infusion in treating liver metastases. PURPOSE: This randomized phase III trial is studying intravenous infusion of fotemustine to see how well it works compared to hepatic arterial infusion of fotemustine in treating patients with unresectable liver metastases from eye melanoma.

Detailed Description
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OBJECTIVES: Primary Compare overall survival of patients with surgically incurable or unresectable liver metastases secondary to uveal melanoma treated with fotemustine administered as an intravenous infusion vs an intra-arterial hepatic perfusion. Secondary Compare progression-free survival of patients treated with this drug. Compare the response rate in patients treated with this drug. Compare the duration of objective response in patients treated with this drug. Compare the patterns of progression in patients treated with this drug. Compare treatment-related toxic effects and catheter-related complications in patients treated with this drug. OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, lactic dehydrogenase level (normal vs abnormal), and WHO performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive fotemustine IV over 1 hour on days 1, 8, and 15 (induction course). Beginning on day 50, patients receive maintenance courses of fotemustine IV over 1 hour every 21 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive fotemustine by a 4-hour intra-arterial (IA) hepatic perfusion on days 1, 8, 15, and 22 (induction course). Beginning on day 57, patients receive maintenance courses of fotemustine by a 4-hour IA hepatic perfusion every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 9 weeks for survival. PROJECTED ACCRUAL: A total of 262 patients (131 per treatment arm) will be accrued for this study within 3 years.

Official Title
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Intravenous Versus Intra-Arterial Fotemustine Chemotherapy in Patients With Liver Metastases From Uveal Melanoma: A Randomized Phase III Study of the EORTC Melanoma Group

Conditions
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Intraocular Melanoma, Metastatic Cancer

Intervention / Treatment
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* Drug: fotemustine
* Drug: isolated perfusion


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed liver metastases secondary to uveal melanoma Surgically incurable or unresectable disease No detectable extrahepatic metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Hepatic Bilirubin < 1.5 times upper limit of normal (ULN) ALT and AST < 5 times ULN Alkaline phosphatase < 5 times ULN Gamma-glutamyltransferase < 5 times ULN Lactic dehydrogenase < 5 times ULN Renal BUN < 1.5 times ULN Creatinine ≤ 1.5 times ULN Cardiovascular No uncontrolled angina pectoris No myocardial infarction within the past 6 months No uncontrolled high blood pressure No evolutive intracranial hypertension No other severe cardiac disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active gastroduodenal ulcer No diabetes No active or uncontrolled infection No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up No other uncontrolled severe medical condition No other malignancy within the past 5 years except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunologic or biologic therapy Chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy for metastatic disease No concurrent radiotherapy Surgery Recovered from prior major surgery Other No prior antineoplastic drugs for metastatic disease More than 4 weeks since prior investigational drugs No other concurrent anticancer agents or therapies

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fotemustine|nan|
|Drug: isolated perfusion|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Best response as assessed by RECIST criteria |  |  | 
| Duration of response |  |  | 
| Toxicity as assessed by CTCAE v3 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver metastases, ciliary body and choroid melanoma, medium/large size, iris melanoma, extraocular extension melanoma, recurrent intraocular melanoma, metastatic intraocular melanoma