PEG-Interferon Alfa-2b in Treating Patients With Stage IV Melanoma

OBJECTIVES:

- Determine the ability of low-dose PEG-interferon alfa-2b to suppress plasma basic
fibroblast growth factor (b-FGF) levels to normal in patients with metastatic melanoma
over-expressing b-FGF.

- Determine the antitumor effect of this drug, in terms of progression-free and overall
survival and tumor response, in these patients.

- Correlate tumor activity of this drug with b-FGF and vascular endothelial growth factor
levels in the plasma and urine of these patients.

- Determine the safety profile of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues
until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly
dose is reached. If there is disease progression, patients then discontinue treatment. If
there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to
1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 2 years.

Inclusion criteria:

- Histologically confirmed stage IV melanoma

- Stage M1a, M1b, or M1c

- Mucosal, ocular, or unknown primary melanoma

- Previously untreated OR received up to 3 prior systemic therapy regimens (excluding
vaccine therapy) for metastatic disease

- Plasma basic fibroblast growth factor level at least 15 pg/mL

- Measurable or evaluable disease

- Central nervous system (CNS) involvement allowed provided CNS directed therapy has
been given and disease has been clinically stable for ≥ 3 months

- Brain computed tomography (CT) scan or Magnetic resonance imaging (MRI) to
confirm stable disease required ≤ 4 weeks prior to study entry

- Age: 18 and over

- ECOG Performance status of 0-2

- Life expectancy at least 6 months

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8 g/dL (transfusions allowed)

- Bilirubin no greater than 2 times upper limit of normal (ULN)

- Alanine Aminotransferase (ALT) no greater than 2 times ULN

- Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min

- At least 4 weeks since prior interferon in the adjuvant or metastatic setting

- At least 4 weeks since prior chemotherapy in the adjuvant or metastatic setting

- At least 4 weeks since prior endocrine therapy in the adjuvant or metastatic setting

- At least 4 weeks since prior radiotherapy in the adjuvant or metastatic setting

- At least 4 weeks since prior surgery in the adjuvant or metastatic setting

- At least 4 weeks since other prior therapy in the adjuvant or metastatic setting

- Negative pregnancy test

- Fertile patients must use effective contraception

Exclusion criteria:

- Myocardial infarction within the past 6 months

- Other active malignancy within the past 5 years except curatively treated basal cell
or squamous cell skin cancer or carcinoma in situ of the cervix

- Other concurrent illness that would preclude study participation

- History of severe depression

- Pregnant or nursing