Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Locally Advanced Melanoma of the Arm or Leg

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Melphalan

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:

• 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