Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma
Condition: Intraocular Melanoma; Melanoma (Skin); Metastatic Cancer
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving
      melphalan directly into the arteries around the tumor may kill more tumor cells. It is not
      yet known whether hepatic arterial infusion with melphalan is more effective than standard
      therapy in treating liver metastases due to melanoma.

      PURPOSE: This randomized phase III trial is studying hepatic arterial infusion with melphalan
      to see how well it works compared to standard therapy in treating patients with unresectable
      liver metastases due to melanoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the hepatic progression-free survival of patients with unresectable liver
           metastases secondary to ocular or cutaneous melanoma treated with percutaneous isolated
           hepatic arterial perfusion (PHP) with melphalan with subsequent venous hemofiltration vs
           the best alternative standard treatment.

      Secondary

        -  Determine the response rate and duration of response in patients treated with melphalan
           PHP.

        -  Determine the patterns of recurrence in patients treated with melphalan PHP.

        -  Compare the overall survival of patients treated with these regimens.

        -  Compare the safety and tolerability of these regimens in these patients.

        -  Determine the pharmacokinetics of melphalan after PHP.

      OUTLINE: This is a multicenter study. Patients are stratified according to site of disease
      (ocular vs cutaneous). Patients are randomized to 1 of 2 treatment arms.

        -  Arm I: Patients undergo an isolated hepatic arterial infusion of melphalan over 30
           minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of
           disease progression or unacceptable toxicity. Patients with complete or partial response
           undergo 2 additional courses in the absence of ongoing or increasing toxicity.

        -  Arm II: Patients receive the best alternative therapy comprising supportive care,
           systemic or regional chemotherapy, hepatic artery (chemo)-embolization, or any other
           appropriate therapy at the National Cancer Institute or therapy at the discretion of
           their physician. Patients may cross over to arm I if they have evidence of disease
           progression.

      Blood samples are collected periodically for pharmacokinetic analysis of melphalan.

      After completion of study treatment, patients are followed periodically for 4 years and then
      annually for survival.

      PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.
    

Intervention name(s): melphalan; regional chemotherapy; systemic chemotherapy; hepatic artery embolization
Intervention type(s): Drug; Drug; Drug; Procedure
Intervention description(s): Given throug isolated hepatic artery infusion; Patients receive the best alternative therapy; Patients receive the best alternative therapy; Patients receive the best alternative therapy
Intervention MeSH terms: Melphalan
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: liver metastases; extraocular extension melanoma; stage IV melanoma; recurrent melanoma; recurrent intraocular melanoma; metastatic intraocular melanoma; iris melanoma; ciliary body and choroid melanoma, medium/large size