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About
Randomized phase III trial to compare the effectiveness of hyperthermic isolated limb perfusion of melphalan with or without tumor necrosis factor in treating patients who have locally advanced melanoma of the arm or leg. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Heating melphalan to several degrees above body temperature and infusing it only to the area around the tumor may kill more tumor cells. It is not yet known whether combining melphalan with tumor necrosis factor is more effective than melphalan alone in treating melanoma.
Full description
OBJECTIVES:
I. Compare hyperthermic isolated limb perfusion with melphalan with or without tumor necrosis factor, in terms of response proportion for lesions in the perfusion field, in patients with locally advanced extremity melanoma.
II. Compare the local recurrence-free survival, improvement in regional symptoms related to tumor, and overall survival in patients treated with these regimens.
III. Compare the toxicity of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor burden (high vs low), prior reperfusion (melphalan vs other), regional nodal site (yes vs no), and participating center. Patients are randomized to one of two treatment arms.
ARM I: Patients undergo hyperthermic isolated perfusions of the lower limb by either the external iliac vessels or the common femoral vessels. Patients undergo perfusions of the upper extremity by the axillary artery and vein using an infraclavicular/axillary incision. Melphalan is introduced into the perfusion by slow injection over 5 minutes and allowed to remain for a total of 60 minutes.
ARM II: Patients undergo hyperthermic isolated perfusions as in arm I. Tumor necrosis factor is administered by slow injection into the arterial line and allowed to remain for a total of 90 minutes. Melphalan is introduced into the perfusion as in arm I and allowed to remain for a total of 60 minutes.
Patients are followed within 6 weeks, at 3, 6, and 12 months, every 6 months for 4 years, and then annually thereafter.
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Inclusion and exclusion criteria
Inclusion Criteria:
Histologically proven locally advanced melanoma of an extremity
One or more evaluable in-transit metastases
All disease within the perfusion field of the extremity (with no local resection options short of amputation)
Disease outside of perfusion field (with no local resection options short of amputation) if all the following are true:
At least 1 bidimensionally measurable lesion
Patients who received prior prophylactic isolated limb perfusion (ILP) must have 1 of the following:
Patients who received prior therapeutic ILP must have 1 of the following:
Performance status - ECOG 0-2
Performance status - Zubrod 0-2
See Disease Characteristics
Platelet count at least 100,000/mm^3
WBC greater than 2,500/mm^3
Hemoglobin greater than 9 g/dL
Bilirubin less than 1.25 times ULN
AST and ALT less than 2 times ULN
Alkaline phosphatase less than 2 times ULN
Coagulation studies normal or within 1 second of upper limit of normal (ULN)
Creatinine less than 1.5 mg/dL
Creatinine clearance greater than 50 mL/min
Calcium less than 12 mg/dL
No severe peripheral vascular disease (claudication or other ischemic peripheral vascular disease [e.g., venous thrombosis or occlusive peripheral arterial disease])
No New York Heart Association class II-IV heart disease (congestive heart failure)
No uncontrolled or life-threatening cardiac arrhythmia
No myocardial infarction within the past year
No unstable angina
No symptomatic cerebral or carotid artery disease
No pulmonary embolism within the past year
Other prior malignancy allowed if completed curative therapy, disease-free for at least 5 years, and at low risk for recurrence
No active peptic ulcer disease within the past year
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known melphalan hypersensitivity
No known hypersensitivity to any component of tumor necrosis factor alpha formulation
No contraindications to ionotropic agents (e.g., dopamine or neosynephrine)
No concurrent infections uncontrolled with antibiotics
HIV negative
At least 1 month since prior biologic therapy
See Disease Characteristics
At least 1 month since prior chemotherapy
At least 4 months since prior isolated limb perfusion
At least 1 month since prior radiotherapy
See Disease Characteristics
At least 12 months since prior coronary artery surgery or angioplasty
Primary purpose
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Interventional model
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216 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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