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
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
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Disease-free survival (DFS)
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%.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|Anne Arundel Medical Center||Annapolis, Maryland 21401|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|University of Texas Southwestern Medical Center||Dallas, Texas|