Azacitidine and Interferon Alfa in Treating Patients With Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Interferon alfa may interfere with the growth of tumor cells. Giving azacitidine together with interferon alfa may be an effective treatment for melanoma. PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine when given together with interferon alfa in treating patients with metastatic melanoma.

Detailed Description
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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.

Official Title
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A Phase I Study of 5-azacytidine (Vidaza) With Interferon α2b in Metastatic Melanoma Patients

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: recombinant interferon alfa-2b
* Drug: azacitidine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant interferon alfa-2b|nan|
|Drug: azacitidine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  |  | 
| Toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  |  | 
| Survival at day 1, 12 months, 3 years, and 5 years |  |  | 
| Relapse-free survival |  |  | 
| Time to relapse |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, stage IV melanoma