Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Delcath Systems Inc.
ClinicalTrials.gov Identifier:
NCT00324727
First received: May 10, 2006
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Intraocular Melanoma
Melanoma (Skin)
Metastatic Cancer
Drug: melphalan
Drug: regional chemotherapy
Drug: systemic chemotherapy
Procedure: hepatic artery embolization
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Delcath Systems Inc.:

Primary Outcome Measures:
  • Hepatic progression free survival [ Time Frame: Treatment to time of progression ] [ Designated as safety issue: No ]

Enrollment: 93
Study Start Date: February 2006
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: melphalan
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 therapy
Drug: systemic chemotherapy
Patients receive the best alternative therapy
Procedure: hepatic artery embolization
Patients receive the best alternative therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed liver metastases secondary to cutaneous or ocular melanoma

    • Unresectable disease
    • Predominantly in the parenchyma of the liver
  • Measurable disease by CT scan and/or MRI
  • Limited unresectable extrahepatic disease allowed provided the life-limiting component of progressive disease is in the liver, including, but not limited to, any of the following:

    • Up to 4 pulmonary nodules, each < 1 cm in diameter
    • Retroperitoneal lymph nodes < 3 cm in diameter
    • Less than 10 skin or subcutaneous metastases < 1 cm in diameter
    • Asymptomatic bone metastases that are eligible for or have undergone palliative external-beam radiotherapy
    • Solitary metastasis to any site that can be resected

PATIENT CHARACTERISTICS:

  • Life expectancy ≥ 3 months
  • ECOG performance status 0-2
  • Bilirubin < 3.0 mg/dL
  • PT within 2 seconds of upper limit of normal (ULN)
  • AST/ALT ≤ 10 times ULN
  • Platelet count > 75,000/mm^3
  • Hematocrit > 27% (may be achieved with a transfusion)
  • Absolute neutrophil count ≥ 1,300/mm^3
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
  • Fertile patients must use effective contraception
  • Not pregnant or nursing
  • Negative pregnancy test
  • No history of congestive heart failure
  • LVEF ≥ 40%
  • No significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease
  • FEV_1 ≥ 30%
  • DLCO ≥ 40% of predicted
  • Weight ≥ 35 kg
  • No untreated active bacterial infection with systemic manifestations (e.g., malaise, fever, and leucocytosis)
  • No severe allergic reactions to iodine contrast unless reaction can be controlled by antihistamines and/or steroids
  • No known hypersensitivity to melphalan
  • No positive serology for HIV, hepatitis B surface antigen, or hepatitis C antibody (pharmacokinetics portion of the study only)
  • No known latex allergy
  • No Childs B or C cirrhosis
  • No evidence of portal hypertension by history, endoscopy, or radiological study
  • No prior history of gastrinoma

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 1 month since prior chemotherapy, radiotherapy, or biologic therapy for this cancer and recovered
  • No prior regionally delivered melphalan
  • No prior Whipple procedure
  • No concurrent immunosuppressive therapy
  • No concurrent chronic anticoagulation therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324727

Locations
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
Sponsors and Collaborators
Delcath Systems Inc.
Investigators
Principal Investigator: Marybeth S. Hughes, MD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Responsible Party: Delcath Systems Inc.
ClinicalTrials.gov Identifier: NCT00324727     History of Changes
Obsolete Identifiers: NCT00291252
Other Study ID Numbers: CDR0000468944, NCI-06-C-0088, NCI-P6701
Study First Received: May 10, 2006
Last Updated: October 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Delcath Systems Inc.:
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

Additional relevant MeSH terms:
Neoplasm Metastasis
Melanoma
Uveal Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Melphalan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014