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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response will be calculated based on the 3-month follow-up assessment of presence of absence of complete response. This will be done using the logistic regression model.
Up to 3 months after completion of study treatment
American College of Surgeons
United States: Food and Drug Administration
|American College of Surgeons Oncology Group||Durham, North Carolina 27705|