A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion and Melphalan With and Without Tumor Necrosis Factor in Patients With Localized Advanced Extremity Melanoma

Study start date: March 1, 1999

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: High tumor burden (more than 10 lesions or any single lesion greater than 3 cm) Presence of pain, edema, skin breakdown, or decreased mobility Greater than 80% of known tumor is within extremity perfusion field Life expectancy more than 6 months No brain metastases At least 1 bidimensionally measurable lesion Patients who received prior prophylactic isolated limb perfusion (ILP) must have 1 of the following: Disease-free interval for at least 6 months after prior ILP with melphalan Disease-free interval for at least 3 months after prior ILP with an agent other than melphalan Patients who received prior therapeutic ILP must have 1 of the following: Partial response of at least 3 months duration after prior ILP with melphalan Stable response or disease progression after ILP without melphalan (performed at least 3 months prior to study) 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