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

NCT ID: NCT00324727

Last Updated: 2021-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2012-08-31

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.

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.

Conditions

Intraocular Melanoma; Melanoma (Skin); Metastatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

melphalan

Intervention Type: DRUG

Given throug isolated hepatic artery infusion

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.

Group Type: ACTIVE_COMPARATOR

regional chemotherapy

Intervention Type: DRUG

Patients receive the best alternative therapy

systemic chemotherapy

Intervention Type: DRUG

Patients receive the best alternative therapy

hepatic artery embolization

Intervention Type: PROCEDURE

Patients receive the best alternative therapy

Interventions

melphalan

Given throug isolated hepatic artery infusion

Intervention Type: DRUG

regional chemotherapy

Patients receive the best alternative therapy

Intervention Type: DRUG

systemic chemotherapy

Patients receive the best alternative therapy

Intervention Type: DRUG

hepatic artery embolization

Patients receive the best alternative therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Delcath Systems Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marybeth S. Hughes, MD

Role: PRINCIPAL_INVESTIGATOR

NCI - Surgery Branch

Locations

John Wayne Cancer Institute at Saint John's Health Center

Santa Monica, California, United States

Swedish Medical Center

Englewood, Colorado, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Carol G. Simon Cancer Center at Morristown Memorial Hospital

Morristown, New Jersey, United States

Cancer Center of Albany Medical Center

Albany, New York, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

St. Luke's Cancer Network at St. Luke's Hospital

Bethlehem, Pennsylvania, United States

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

Related Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185532/

Publication of Results

Other Identifiers

NCI-06-C-0088

Identifier Type: -

Identifier Source: secondary_id

NCI-P6701

Identifier Type: -

Identifier Source: secondary_id

CDR0000468944

Identifier Type: -

Identifier Source: org_study_id

NCT00291252

Identifier Type: -

Identifier Source: nct_alias