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

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00324727

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
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:

Genetics Home Reference related topics: retinoblastoma

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate and duration of response [ Designated as safety issue: No ]
Patterns of recurrence [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Safety and tolerability [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	February 2006

Arms	Assigned Interventions
Arm I: Experimental 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
Arm II: Active Comparator 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

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Marybeth S. Hughes, MD

NCI - Surgery Branch

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000468944, NCI-06-C-0088, NCI-P6701
Study First Received:	May 10, 2006
Last Updated:	November 16, 2009
ClinicalTrials.gov Identifier:	NCT00324727 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

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:

Melphalan
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Melanoma
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Neoplasm Metastasis

Nevi and Melanomas
Alkylating Agents
Neoplasms by Histologic Type
Eye Neoplasms
Eye Diseases
Immunosuppressive Agents
Pharmacologic Actions
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on February 04, 2010