RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. Combining hyperthermia with chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of melphalan and whole-body hyperthermia in treating patients with advanced melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma stage III melanoma Recurrent Melanoma	Drug: melphalan	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the combination of 41.8 degrees Celsius whole body hyperthermia (WBH) and melphalan (L-PAM) in patients with advanced melanoma.

II. Assess the efficacy of this combination of therapy.

III. Assess the clinical toxicity of WBH and L-PAM in these patients.

IV. Obtain pilot data on the effect of WBH and L-PAM on cytokine induction in these patients.

PROTOCOL OUTLINE: The combination of whole body hyperthermia (WBH) and melphalan (L-PAM) is administered on week 1. The infusion of L-PAM is administered at a constant rate over approximately 10 minutes, beginning 20 minutes after achieving target temperature of 41.8 degrees Celsius by esophageal or axillary temperature probe. WBH is continued for an additional 40 minutes for a total of 60 minutes. On week 5 or 6, patients receive another combination of WBH and L-PAM.

Disease status is reevaluated at least every 2 courses. Patients without progressive disease continue therapy of WBH and L-PAM every 4 weeks for a maximum of 6 courses.

PROJECTED ACCRUAL: Approximately 34 patients will be accrued for this study.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced melanoma beyond hope of surgical cure or metastatic disease
• Tumors must be refractory to all known forms of effective therapy
• No CNS tumor involvement
• No major liver involvement (more than 33% replacement of liver by tumor)

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since biologic therapy
• Chemotherapy: At least 8 weeks since nitrosoureas (e.g., lomustine, carmustine, mitomycin); At least 4 weeks since any other chemotherapy; Recovered from all toxic effects; No concurrent chemotherapy
• Endocrine therapy: At least 4 weeks since endocrine therapy; No concurrent hormonal therapy
• Radiotherapy: At least 4 weeks since radiotherapy; No prior irradiation of more than 25% of the marrow
• Surgery: Not specified
• Other: No concurrent nonsteroidal antiinflammatory agents or aspirin

--Patient Characteristics--

• Age: 16 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: WBC greater than 3,000/mm3; Absolute granulocyte count at least 1,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; Alkaline phosphatase no greater than 3 times normal; SGOT no greater than 3 times normal; Protein no less than 15% below lower limit of normal
• Renal: BUN less than 30 mg/dL; Creatinine less than 1.5 mg/dL OR Creatinine clearance no less than 60 mL/min; Calcium no greater than 11.0 mg/dL; Sodium 130-150 mEq/L; Potassium 3.0-5.0 mg/dL
• Cardiovascular: No organic heart disease, including: coronary artery disease; history of angina; history of dysrhythmia requiring ongoing medical intervention; uncontrolled hypertension; patients requiring beta blockers
• Neurologic: No moderate or severe peripheral neuropathy; No history of severe emotional instability by psychiatric history
• Pulmonary: FEV1 at least 60% of predicted; Maximum voluntary volume at least 60% of predicted; Partial pressure of oxygen at least 60 OR Oxygen saturation at least 90%
• Other: No history of secondary primary cancer which conceivably could be active; No active nonmalignant gastric and/or duodenal ulcer; No serious infection requiring hospitalization within the previous 14 days; No history of hepatitis related to general anesthesia; No history of allergy to lidocaine or related compounds; No development of malignant hyperthermia after general anesthesia; No unexplained persistent fever; Not pregnant or nursing

Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Study chairs or principal investigators

H. Ian Robins,  Study Chair,  University of Wisconsin Comprehensive Cancer Center   

Study ID Numbers:  CDR0000065487; WCCC-CO-9571; NCI-G97-1216
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002973
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08