Azacitidine and Recombinant Interferon Alfa-2b in Treating Patients With Stage III or Stage IV Melanoma or Stage IV Kidney Cancer That Cannot Be Removed By Surgery
This phase I trial is studying the side effects and best dose of recombinant interferon alfa-2b when given together with azacitidine in treating patients with stage III or stage IV melanoma or stage IV kidney cancer that cannot be removed by surgery. 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. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. Giving azacitidine together with recombinant interferon alfa-2b may kill more tumor cells.
Recurrent Renal Cell Cancer
Stage III Melanoma
Stage IV Melanoma
Stage IV Renal Cell Cancer
Biological: recombinant interferon alfa-2b
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma|
- Adverse event profile of azacitidine and recombinant interferon alfa-2b in patients with unresectable or metastatic melanoma and renal cell carcinoma [ Time Frame: Continuously throughout study ] [ Designated as safety issue: Yes ]Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
- Maximum tolerated dose of recombinant interferon alfa-2b when administered in combination with 5-azacitidine [ Time Frame: Course 1 (4 weeks) ] [ Designated as safety issue: Yes ]Toxicity will be graded according to the NCI CTCAE version 3.0. The MTD is the highest dose level in which < 2 patients of 6 develop first cycle DLT.
- Correlation of promoter methylation with the level of expression of the genes [ Time Frame: Day 5 or 8 and 24 or 26 of course 1 ] [ Designated as safety issue: No ]Determined by Western blotting, immunohistochemistry, and/or RT-PCR. We will use Western blot analysis when antibodies are available and semi-quantitative RT-PCR in cases where antibodies are not available.
- Response rate of giving recombinant interferon alfa-2b when administered in combination with 5-azacitidine in patients with metastatic melanoma and renal cell carcinoma [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]Evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
|Study Start Date:||July 2005|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, biological therapy)
Patients receive azacitidine SC once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.
Biological: recombinant interferon alfa-2b
Other Names:Drug: amifostine/azacitidine
I. Determine the adverse event profile and maximum tolerated dose of interferon alfa-2b when combined with azacitidine in patients with unresectable stage III or IV melanoma or unresectable stage IV renal cell carcinoma.
II. Determine the feasibility of this regimen for future phase II trials.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive azacitidine subcutaneously (SC) once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of interferon alfa-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 2-4 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00217542
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520-8032|
|Principal Investigator:||Mario Sznol||Yale University|