Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery
This study combines the DNA methyltransferase inhibitor, 5-azacitidine (5-AZA), with an orally bioavailable histone deacetylase inhibitor, entinostat (SNDX-275), for the adjuvant treatment of patients with resected stage I non-small cell lung cancer NCSLC
Stage IA Non-small Cell Lung Cancer
Stage IB Non-small Cell Lung Cancer
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Disease-free survival (DFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]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%.
- Toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Simple descriptive statistics will be utilized to display the data.
- Median disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis.
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]McNemar's test will be used to compare the change in methylation after treatment in sputum.
- 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 ] [ Designated as safety issue: No ]Kaplan Meier curves will be used.
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
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 Names:Drug: entinostat
Other Names:Other: laboratory biomarker analysis
No Intervention: Arm II (standard of care)
Patients receive standard of care.
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.
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Jhanelle E. Gray 813-745-3050 firstname.lastname@example.org|
|Principal Investigator: Jhanelle E. Gray|
|United States, Maryland|
|Anne Arundel Medical Center||Recruiting|
|Annapolis, Maryland, United States, 21401|
|Contact: Peter R. Graze 410-573-5300 email@example.com|
|Principal Investigator: Peter R. Graze|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21287-8936|
|Contact: Charles M. Rudin 410-502-0678 firstname.lastname@example.org|
|Principal Investigator: Charles M. Rudin|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: James D. Luketich 412-647-2911 email@example.com|
|Principal Investigator: James D. Luketich|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Contact: Leora Horn 615-322-4967 firstname.lastname@example.org|
|Principal Investigator: Leora Horn|
|United States, Texas|
|University of Texas Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Joan H. Schiller 214-648-4180 email@example.com|
|Principal Investigator: Joan H. Schiller|
|Principal Investigator:||Charles Rudin||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|