Trial Information

Phase II Randomized Study of Isolated Limb Perfusion Using Melphalan With or Without Tumor Necrosis Factor in Patients With Unresectable High Grade Soft Tissue Sarcomas of the Extremity

OBJECTIVES: I. Determine the response rates, duration of response, patterns of recurrence
and overall survival in patients with unresectable high grade soft tissue sarcomas of the
extremity following isolated limb perfusion (ILP) using melphalan with or without tumor
necrosis factor (TNF).

II. Determine the application of these regimens as neoadjuvant therapy to render an
unresectable sarcoma resectable.

III. Determine whether either regimen results in durable disease control and limb salvage
for patients with multifocal unresectable high grade soft tissue sarcoma of the extremity or
patients with stage IV soft tissue sarcoma with symptomatic primary extremity tumor.

PROTOCOL OUTLINE: This is a randomized study.

Patients are randomized to 1 of 2 treatment arms:

Arm I: Patients receive isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and
melphalan. After the limb is warmed, TNF is injected into the arterial line of the
extracorporeal ILP circuit over 2-3 minutes beginning at time 0, and perfusion proceeds for
another 25 minutes. Melphalan is injected into the same line over 3-5 minutes and perfusion
with both drugs continues for another 60 minutes.

Arm II: Patients receive ILP with melphalan alone. Melphalan is injected into the arterial
line of the extracorporeal ILP circuit over 3-5 minutes beginning approximately 30 minutes
after initiation of perfusion as in arm I, and perfusion proceeds for 60 minutes.

Patients with potentially curable localized disease undergo a definitive local resection
4-12 weeks following ILP at the time of maximum tumor response as determined by physical
exam and CT or MRI. Patients with microscopically positive viable tumor margins following
resection receive adjuvant external beam radiotherapy as clinically indicated. If
definitive local control cannot be confirmed with either local excision or biopsies, then
amputation is recommended in the absence of unresectable metastatic disease. Local
resection may also be performed on patients who achieve partial response. Patients with
unresectable metastatic pulmonary disease who are undergoing ILP for palliative purposes do
not undergo definitive resection.

Patients are followed at 4-6 weeks, every 3 months for 2 years, and then every 4 months
thereafter in the absence of disease progression. Patients expected to undergo interval
resection are followed every 4 weeks until the procedure is scheduled.

PROJECTED ACCRUAL:

A total of 12-40 patients (6-20 per arm) will be accrued for this study.