Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates
I. To assess toxicities of decitabine plus escalating doses of pegylated interferon alfa-2b
(PEG-Intron) in patients with metastatic solid tumor.
II. To identify the dose-limiting toxicity of decitabine in combination with escalating
doses of pegylated interferon alfa-2b in these patients.
III. To identify the maximum tolerated dose of pegylated interferon alfa-2b in combination
with decitabine in these patients.
I. To evaluate pretreatment and post-treatment blood and tumor samples to identify changes
in global (genomic) DNA methylation.
II. To evaluate pretreatment and post-treatment blood, skin and tumor samples to identify
changes in Mage-1 mRNA and protein expression, DNMT-1 levels (due to sequestration by
5-azacytidine), p53 induction (evidence of DNA damage response), as well as changes in
levels of 2'5'-oligoadenylate synthesis, MxA and HLA class I as indicators of interferon
III. To evaluate complete and partial response rates in patients receiving decitabine in
combination with escalating doses of pegylated interferon alfa-2b.
This is a dose-escalation study of pegylated interferon alfa-2b. Patients are assigned to 1
of 2 treatment groups.
GROUP 1 (control): Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients who experience disease progression after the first course of treatment may
crossover to receive treatment in group 2.
GROUP 2: Patients receive decitabine as in group 1 and pegylated interferon alfa-2b
subcutaneously on days 1, 8, 15, and 22.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample, normal skin, and tissue biopsy collection at baseline and
periodically during study. Blood, normal skin, and tissue samples are analyzed for global
(genomic) DNA methylation (gene-promoter methylation, gene and protein expression, p53
induction by DNA damage) and interferon levels by high-performance (pressure) liquid
chromatography and PCR methylation assays, and for pharmacodynamic studies.
After completion of study treatment, patients are followed at 28 days and then every 3
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
The type, frequency, and severity of each toxicity will be reported.
At each dose level of PEGIntron and decitabine
Nevada Cancer Institute-Summerlin Campus
United States: Food and Drug Administration
|Nevada Cancer Institute-Summerlin Campus||Las Vegas, Nevada 89135|