Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors
|ClinicalTrials.gov Identifier: NCT00701298|
Recruitment Status : Terminated
First Posted : June 19, 2008
Last Update Posted : February 24, 2014
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Adult Solid Tumor, Protocol Specific||Biological: peginterferon alfa-2b Drug: decitabine Other: laboratory biomarker analysis||Phase 1|
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 response.
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 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||October 2010|
Active Comparator: Group 1 (chemotherapy)
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 whose disease is not responding after the first course may crossover to group 2.
Other: laboratory biomarker analysis
Experimental: Group 2 (chemotherapy and antineoplastic agent)
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.
Biological: peginterferon alfa-2b
Other: laboratory biomarker analysis
- Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 28 days ]The type, frequency, and severity of each toxicity will be reported.
- Dose-limiting toxicity (DLT) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0 [ Time Frame: First 28-day course ]DLT is defined as grade III drug-related non hematologic and/or grade IV drug-related hematologic toxicity.
- Maximum-tolerated dose (MTD) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0 [ Time Frame: First 28-day course ]The MTD will be the dose level where not more than 1 case of a specific grade III-IV drug-related toxicity is observed, and either 2+toxicities have been observed at the next highest dose level, or the maximum dose-level of PEG-Intron has been reached.
- Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC) [ Time Frame: Baseline to up to day 1 of course 2 ]Repeated measures analysis of variance and other linear modeling techniques will be used.
- Changes in expression of methylation-regulated genes in human biological tissues [ Time Frame: Baseline to up to day 1 of course 2 ]Repeated measures analysis of variance and other linear modeling techniques will be used.
- Complete and partial response rates [ Time Frame: Up to 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00701298
|United States, Nevada|
|Nevada Cancer Institute-Summerlin Campus|
|Las Vegas, Nevada, United States, 89135|
|Principal Investigator:||Wolfram Samlowski||Nevada Cancer Institute-Summerlin Campus|