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

Phase II Study of Low Dose Peginterferon Alfa-2b in Patients With Metastatic Melanoma Over-Expressing Basic Fibroblast Growth Factor

RATIONALE: Peginterferon (PEG-interferon) alfa-2b may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase II trial to study the effectiveness of PEG-interferon alfa-2b in treating patients who have 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