Protocol Number: 03-C-0137

Title:

Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion and Melphalan with or without Tumor Necrosis Factor in the Patient with Localized, Advanced, Extremity Melanoma

Number:

03-C-0137

Summary:

This study, conducted by the American College of Surgeons Oncology Group, will examine the safety and effectiveness of adding tumor necrosis factor (TNF) to a regimen of hyperthermic isolated limb perfusion (ILP) plus chemotherapy for treating melanoma in an arm or leg. With ILP, chemotherapy is given in high concentrations directly into the main blood vessels supplying the affected limb. The drugs circulate through the blood vessels for a short time and are then flushed out of the body. Before giving the drugs, the blood in the limb is heated in a process called hyperthermia to enhance the drugs' effectiveness. The anti-cancer drug melphalan is used in standard hyperthermic ILP treatment. This study will see if adding TNF to the treatment regimen can enhance tumor shrinkage and prolong disease remission. It will also compare the side effects and long-term effects of the two treatments.

Patients 18 years of age or older with advanced melanoma in an arm or leg may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, electrocardiogram, tumor biopsy, Computed Tomography (CT) imaging scans of the chest, abdomen, pelvis and brain, and a magnetic resonance imaging (MRI) scan of the brain. Whole body scans will be done, if needed. These tests will be done within 90 days of starting treatment.

Participants will be randomly assigned to one of two treatment groups. Group 1 will receive ILP with hyperthermia using melphalan. Group 2 will receive ILP with hyperthermia using melphalan and TNF. All participants will receive hyperthermia under general anesthesia in the operating room. Tubes will be inserted into a vein in the neck or under the collarbone and then into blood vessels leading to the affected limb. A machine like the one used in open-heart surgery will circulate the blood and the drugs through these tubes during the procedure. A tourniquet will be placed on the limb to keep the drugs from entering the blood supply to the rest of the body. The blood from the limb will be heated to 102(Infinite) F to 105(Infinite) F (about the temperature of a hot tub) while it circulates through the machine. A radioactive chemical will be put in the blood to see how much of the drugs get into the blood supply and if any drug leaks to the rest of the body. In patients with melanoma in the leg, the lymph nodes in the groin will be removed if the cancer has spread to those nodes. In patients with melanoma in an arm, lymph nodes in the armpit will be removed whether or not they appear to contain cancer cells. Patients' heart and blood pressure will be monitored closely for 1 to 2 days, and total hospitalization time will be 4 to 8 days. In addition to treatment, patients will undergo the following tests before ILP and at various intervals after the procedure:

- Measurements, photographs and biopsies of tumor deposits in the affected limb;

- Ultrasound, CT scan or MRI of the affected limb for measurement of deep-lying tumors;

- Referral to cardiologist for examination and tests, as needed, in patients 40 years old or older;

- Pregnancy test for women of child-bearing potential.

If needed, patients will have ultrasound of the limb within a few days after treatment to look for blood clots. Patients receiving TNF will have blood samples collected from the affected limb before and after TNF is given to measure TNF blood levels. Patients will be followed for the rest of their life to determine long-term effects of the study procedures.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Follow-up Of Previously Enrolled Subjects Only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions: Currently Not Provided

Disease Category:

PROTICD

Keywords:

Clinical Response

Regional Therapy

Treatment Toxicity

Recurrence Free Survival

Overall Survival

Recruitment Keywords:

Melanoma

Metastatic Melanoma

Extremity Melanoma

Conditions:

Malignant Melanoma

Investigational Drug(s):

TNF

Investigational Device(s):

None

Contacts:

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citations:

Asher A, Mule JJ, Reichert CM, Shiloni E, Rosenberg SA.

Studies on the anti-tumor efficacy of systemically administered recombinant tumor necrosis factor against several murine tumors in vivo. J Immunol. 1987 Feb 1;138(3):963-74.

Barker WC, Andrich MP, Alexander HR, Fraker DL. Continuous intraoperative external monitoring of perfusate leak using iodine-131 human serum albumin during isolated perfusion of the liver and limbs. Eur J Nucl Med. 1995 Nov;22(11):1242-8.

Bartsch HH, Pfizenmaier K, Schroeder M, Nagel GA. Intralesional application of recombinant human tumor necrosis factor alpha induces local tumor regression in patients with advanced malignancies. Eur J Cancer Clin Oncol. 1989 Feb;25(2):287-91.

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