Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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

Further Study Information

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Eligibility Criteria

Inclusion Criteria:

• Patients must be status post complete (R0) surgical resection of pathologically-proven NSCLC (stage IA-IB according to AJCC version 7)

• Patients must be at least 4 weeks out from completion of surgery

• ECOG performance status =< 2

• Absolute neutrophil count >= 1,000/mcL

• Platelets >= 100,000/mcL

• Total bilirubin =< 1.5 X institutional upper limit of normal

• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

• Creatinine =< 1.5 X institutional upper limit of normal

• The effects of entinostat and 5-azacitidine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients must be within 8 weeks of completing surgery

• Patients who have received prior chemotherapy or radiation for treatment of their current diagnosis of lung cancer

• Patients with sub-lobar resections (ie: wedge resection or segmentectomy)

• Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided tumors)

• Patients may not be receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-azacitidine or other agents used in the study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because entinostat and 5-azacitidine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat or 5-azacitidine, breastfeeding should be discontinued if the mother is treated on this protocol; these potential risks may also apply to other agents used in this study

• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with entinostat or 5-azacitidine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Charles Rudin

Principal Investigator

U.S.A.
Florida
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Jhanelle E. Gray	Ph: 813-745-3050
			Email: jhanelle.gray@moffitt.org
		Jhanelle E. Gray	Principal Investigator
Maryland
	Annapolis
	DeCesaris Cancer Institute at Anne Arundel Medical Center
		Peter R. Graze	Ph: 410-573-5300
			Email: pgraze@aahs.org
		Peter R. Graze	Principal Investigator
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Charles M. Rudin	Ph: 410-502-0678
			Email: rudin@jhmi.edu
		Charles M. Rudin	Principal Investigator
Pennsylvania
	Pittsburgh
	UPMC Cancer Centers
		James D. Luketich	Ph: 412-647-2911
			Email: luketichjd@upmc.edu
		James D. Luketich	Principal Investigator
Tennessee
	Nashville
	Vanderbilt-Ingram Cancer Center
		Leora Horn	Ph: 615-322-4967
			Email: leora.horn@vanderbilt.edu
		Leora Horn	Principal Investigator
Texas
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Joan H. Schiller	Ph: 214-648-4180
			Email: joan.schiller@utsouthwestern.edu
		Joan Hoff Schiller	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01207726
Information obtained from ClinicalTrials.gov on January 13, 2013

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