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

• ClinicalTrials.gov Identifier: NCT00324727
• Recruitment Status: Completed
• First Posted: May 11, 2006
• Last Update Posted: June 21, 2021
• Sponsor: Delcath Systems Inc.
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Delcath Systems Inc.

Study Description

Brief 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.

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

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (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
• Study Start Date: February 2006
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Hepatic progression free survival [ Time Frame: Treatment to time of progression ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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.

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marybeth S. Hughes, MD; NCI - Surgery Branch

More Information

Additional Information:

Publication of Results 

• Responsible Party: Delcath Systems Inc.
• ClinicalTrials.gov Identifier: NCT00324727
• Obsolete Identifiers: NCT00291252
• Other Study ID Numbers: CDR0000468944; NCI-06-C-0088; NCI-P6701
• First Posted: May 11, 2006
• Last Update Posted: June 21, 2021
• Last Verified: June 2021

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:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Melphalan; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs