Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT01207726|
Recruitment Status : Terminated
First Posted : September 23, 2010
Last Update Posted : May 1, 2015
|Condition or disease||Intervention/treatment||Phase|
|Stage IA Non-Small Cell Lung Carcinoma Stage IB Non-Small Cell Lung Carcinoma||Drug: Azacitidine Drug: Entinostat Other: Laboratory Biomarker Analysis||Phase 2|
I. To assess the effect of 5-azacitidine and entinostat on the hazard of 3 year progression-free survival in patients with resected stage I non-small cell lung cancer.
I. To assess the safety, tolerability and toxicity of entinostat and 5-azacitidine in patients with resected stage I non-small cell lung cancer.
II. To explore the effect of entinostat and 5-azacitidine on median disease-free and overall survival in patients with resected stage I non-small cell lung cancer.
III. To assess the pharmacodynamic effects of 5-azacitidine and entinostat on DNA methylation and gene re-expression in patients with resected stage I NSCLC through analysis of sputum.
IV. To estimate the effect of entinostat and 5-azacitidine on progression free survival comparing patients with N2 lymph nodes categorized as methylated pre-treatment with those who are categorized as unmethylated.
V. To establish factors that predict clinical outcome in patients treated with combination epigenetic therapy by performing genome-wide analyses on pre-treatment tumor DNA.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10 and entinostat orally (PO) once daily (QD) on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive standard of care.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-Azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care|
|Study Start Date :||September 2010|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||May 2013|
Experimental: Arm I (azacitidine, entinostat)
Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
No Intervention: Arm II (standard of care)
Patients receive standard of care.
- Disease-free survival (DFS) [ Time Frame: 3 years ]The DFS hazard rate and 95% confidence interval will be reported. At this time, event time distributions for disease-free survival in the two arms will be estimated with the method of Kaplan and Meier and compared using a stratified Cox-proportional hazards model (stratified for stage IA vs IB) with a two-sided alpha of 10%.
- Factors that predict clinical outcome in patients treated with combination epigenetic therapy in terms of epigenomic data generated from the Illumina platform [ Time Frame: Up to 2 years ]
- Median disease-free survival [ Time Frame: Up to 5 years ]Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
- Number of relapses and deaths per total time of follow-up comparing patients with N2 lymph nodes in terms of methylated and unmethylated [ Time Frame: Up to 5 years ]Kaplan Meier curves will be used.
- Overall survival [ Time Frame: Up to 5 years ]Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
- Presence of methylation patterns [ Time Frame: Up to 2 years ]McNemar's test will be used to compare the change in methylation after treatment in sputum.
- Toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 5 years ]Simple descriptive statistics will be utilized to display the data.
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): NCT01207726
|United States, California|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Maryland|
|Anne Arundel Medical Center|
|Annapolis, Maryland, United States, 21401|
|Greater Baltimore Medical Center|
|Baltimore, Maryland, United States, 21204|
|Johns Hopkins Bayview Medical Center|
|Baltimore, Maryland, United States, 21224|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|Principal Investigator:||Charles Rudin||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|