Azacitidine and Entinostat in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT00387465|
Recruitment Status : Completed
First Posted : October 13, 2006
Last Update Posted : May 1, 2015
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Non-Small Cell Lung Carcinoma Stage IIIA Non-Small Cell Lung Cancer Stage IIIB Non-Small Cell Lung Cancer Stage IV Non-Small Cell Lung Cancer||Drug: Azacitidine Drug: Entinostat Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1 Phase 2|
I. To assess safety, characterize toxicities, and determine the maximum tolerated dose of 5-AZA (azacitidine) with a fixed-dose of entinostat in patients with recurrent advanced non-small cell lung cancer (NSCLC). (Phase I) II. To determine the objective response rate of 5-AZA and entinostat in patients with recurrent NSCLC. (Phase II)
I. To determine the pharmacokinetic profile of 5-AZA and entinostat in patients with recurrent NSCLC.
II. To assess the pharmacodynamic effects of 5-AZA and entinostat on deoxyribonucleic acid (DNA) methylation, histone acetylation, and gene re-expression in patients with recurrent NSCLC through analysis of blood, sputum and tissue biopsies.
III. To explore the effect of 5-AZA and entinostat on progression-free and overall survival in patients with recurrent advanced non-small cell lung cancer.
IV. To explore the differing response rates and progression-free survivals of two schedules of 5-AZA and entinostat in patients with recurrent advanced non-small cell lung cancer.
OUTLINE: This is a multicenter, phase I, dose-escalation study of azacitidine followed by an open-label, phase II study.
Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (PO) on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||162 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Entinostat in Combination With 5-Azacytidine in Patients With Recurrent Advanced Non-Small Cell Lung Cancer|
|Study Start Date :||August 2006|
|Actual Primary Completion Date :||July 2014|
|Actual Study Completion Date :||November 2014|
Experimental: Treatment (azacitidine, entinostat)
Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose (MTD) of azacitidine when given together with entinostat, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 (phase I) [ Time Frame: Up to 28 days ]
- Objective response rate after treatment with azacitidine and entinostat using the Response Evaluation Criteria in Solid Tumors (RECIST) (phase II) [ Time Frame: Up to 8 years ]
- Effect of entinostat and azacitidine on DNA methylation patterns and gene expression [ Time Frame: Baseline and days 10 and 29 ]The frequency of significant demethylation and acetylation will be summarized across dosing cohorts of azacitidine. The difference between the methylation indices post-and pre-treatment will be compared using paired Student's t-test. Similar analyses will be performed for the acetylation index. Relationships between changes in gene re-expression and clinical response will be assessed using Fisher's exact tests.
- Effect of entinostat and azacitidine on enhancing response to subsequent therapy [ Time Frame: Up to 8 years ]
- Overall survival [ Time Frame: Up to 1 year ]Determined by the method determined by Kaplan and Meier. 95% confidence intervals will be estimated.
- Pharmacokinetic profile of entinostat and azacitidine [ Time Frame: Baseline, day 1, 10, 15, 17, and 22 ]A Mann-Whitney U test and logistic regression will be used to evaluate the association between azacitidine or entinostat exposure and methylation and acetylation changes expressed as a categorical variable (i.e.: response or no response). The azacitidine exposure parameters explored will be maximum plasma concentrations (Cmax) and area under the concentration-time curve (AUC). The entinostat exposure parameters explored will be Vss.
- Progression-free survival [ Time Frame: Up to 1 year ]Determined by the method determined by Kaplan and Meier. 95% confidence intervals will be estimated.
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): NCT00387465
|United States, California|
|USC Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|Sidney Kimmel Cancer Center|
|San Diego, California, United States, 92121|
|United States, Maryland|
|Johns Hopkins Bayview Medical Center|
|Baltimore, Maryland, United States, 21224|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||John Wrangle||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|