Azacitidine and Interferon Alfa in Treating Patients With Metastatic Melanoma

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of azacitidine in combination with interferon alfa-2b in patients with metastatic melanoma.
• Determine if the MTD of this regimen is biologically active in these patients.
• Define and describe the toxicities associated with this regimen.

Secondary

• Determine, preliminarily, the response in patients treated with this regimen.
• Describe, preliminarily, the time to progression and overall survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of azacitidine.

Patients receive azacitidine subcutaneously (SC) once daily on days 1-5 (week 1) followed by interferon alfa-2b SC 3 days a week in weeks 2-4. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of azacitidine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma
• At least one lesion appropriate for 3 separate punch or core needle biopsies
• Must have received and failed ≥ 1 prior systemic treatment for metastatic disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT < 2 times ULN
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known allergies to azacitidine, interferon alfa, benzyl alcohol, or mannitol
• No uncontrolled infection
• No known HIV positivity
• No hepatitis B or hepatitis C infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 3 weeks since prior systemic therapy
• More than 4 weeks since prior radiotherapy to target lesions with evidence of progression
• No concurrent radiotherapy to target lesions
• No concurrent oral or IV corticosteroids

• Topical creams or ocular steroid drops are allowed