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

Sponsor

Delcath Systems Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00324727

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

7.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Feb 1, 2006

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 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

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

Hepatic progression free survival [Treatment to time of progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	John Wayne Cancer Institute at Saint John's Health Center	Santa Monica	California	United States	90404
2	Swedish Medical Center	Englewood	Colorado	United States	80113
3	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612-9497
4	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
5	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
6	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey	United States	07962-1956
7	Cancer Center of Albany Medical Center	Albany	New York	United States	12208
8	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
9	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
10	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania	United States	18015
11	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
12	University of Texas Medical Branch	Galveston	Texas	United States	77555-0361