Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma
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.
Drug: regional chemotherapy
Drug: systemic chemotherapy
Procedure: hepatic artery embolization
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Random-Assignment Study of Hepatic Arterial Infusion of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) (Delcath System) Versus Best Alternative Care for Ocular and Cutaneous Melanoma Metastatic to the Liver|
- Hepatic progression free survival [ Time Frame: Treatment to time of progression ] [ Designated as safety issue: No ]
|Study Start Date:||February 2006|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Experimental: 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.
Given throug isolated hepatic artery infusion
Active Comparator: 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.
Drug: regional chemotherapy
Patients receive the best alternative therapyDrug: systemic chemotherapy
Patients receive the best alternative therapyProcedure: hepatic artery embolization
Patients receive the best alternative therapy
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00324727
|United States, California|
|John Wayne Cancer Institute at Saint John's Health Center|
|Santa Monica, California, United States, 90404|
|United States, Colorado|
|Swedish Medical Center|
|Englewood, Colorado, United States, 80113|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Tampa, Florida, United States, 33612-9497|
|United States, Maryland|
|Greenebaum Cancer Center at University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|United States, New Jersey|
|Carol G. Simon Cancer Center at Morristown Memorial Hospital|
|Morristown, New Jersey, United States, 07962-1956|
|United States, New York|
|Cancer Center of Albany Medical Center|
|Albany, New York, United States, 12208|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210-1240|
|United States, Oregon|
|Providence Cancer Center at Providence Portland Medical Center|
|Portland, Oregon, United States, 97213-2967|
|United States, Pennsylvania|
|St. Luke's Cancer Network at St. Luke's Hospital|
|Bethlehem, Pennsylvania, United States, 18015|
|UPMC Cancer Centers|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|University of Texas Medical Branch|
|Galveston, Texas, United States, 77555-0361|
|Principal Investigator:||Marybeth S. Hughes, MD||NCI - Surgery Branch|