Pegylated Arginine Deiminase in Treating Patients With Metastatic Melanoma That Cannot Be Removed by Surgery

Clinical Protocol for Phase II Testing of ADI-PEG 20 in Patients With Metastatic Melanoma

RATIONALE: Pegylated arginine deiminase may stop the growth of tumor cells by taking away an amino acid needed for cell growth.

PURPOSE: This phase II trial is studying how well pegylated arginine deiminase works in treating patients with metastatic melanoma that cannot be removed by surgery.

OBJECTIVES:

Primary:

• Determine the clinical response (complete and partial response) in patients with unresectable metastatic melanoma treated with pegylated arginine deiminase.

Secondary:

• Determine the toxicity profile of this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
• Determine the progression-free survival and overall survival of patients treated with this drug.

OUTLINE: Patients receive pegylated arginine deiminase intramuscularly once or twice a week in weeks 1-4. Courses repeat every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are acquired at baseline and every 2 weeks thereafter for pharmacokinetic and pharmacodynamic studies.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 5 years, and annually thereafter.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma, meeting any of the following criteria:

  • Progressive disease after chemotherapy, radiotherapy, surgery, or immunotherapy
  • No longer responding to standard therapy OR have refused standard therapy

• Unresectable disease

• Measurable or evaluable disease

• No clinical ascites

• No symptomatic pleural effusion

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 12 weeks
• Karnofsky performance status 70-100%
• Bilirubin ≤ 3.0 mg/dL
• Albumin ≥ 3.0 g/dL
• Alkaline phosphatase < 5 times upper limit of normal (ULN)
• Serum glucose > 60 mg/dL
• Amylase < 1.5 times ULN
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• No New York Heart Association class III-IV heart failure
• No serious infection requiring treatment with antibiotics
• No known allergy to E. coli drug products (e.g., sargramostim [GM-CSF])
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 forms of effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior anticancer therapy
• At least 4 weeks since prior surgery and recovered
• No concurrent participation in another investigational drug study