Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma
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|ClinicalTrials.gov Identifier: NCT00324727|
Recruitment Status : Completed
First Posted : May 11, 2006
Last Update Posted : June 21, 2021
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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|
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||93 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (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|
|Study Start Date :||February 2006|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||August 2012|
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.
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
- Hepatic progression free survival [ Time Frame: Treatment to time of progression ]
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|Ages Eligible for Study:||18 Years to 120 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00324727
|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|
|Principal Investigator:||Marybeth S. Hughes, MD||NCI - Surgery Branch|
|Responsible Party:||Delcath Systems Inc.|
|Other Study ID Numbers:||
|First Posted:||May 11, 2006 Key Record Dates|
|Last Update Posted:||June 21, 2021|
|Last Verified:||June 2021|
extraocular extension melanoma
stage IV melanoma
recurrent intraocular melanoma
metastatic intraocular melanoma
ciliary body and choroid melanoma, medium/large size
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs