|Phase II||Biomarker/Laboratory analysis, Treatment||Active||18 and over||NCI||NCI-2012-02901|
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
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.
- 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
- 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 Lead Organizations/Sponsors
National Cancer Institute
|Charles Rudin||Principal Investigator|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Jhanelle E. Gray||Ph: 813-745-3050|
|Jhanelle E. Gray||Principal Investigator|
|DeCesaris Cancer Institute at Anne Arundel Medical Center|
|Peter R. Graze||Ph: 410-573-5300|
|Peter R. Graze||Principal Investigator|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Charles M. Rudin||Ph: 410-502-0678|
|Charles M. Rudin||Principal Investigator|
|UPMC Cancer Centers|
|James D. Luketich||Ph: 412-647-2911|
|James D. Luketich||Principal Investigator|
|Vanderbilt-Ingram Cancer Center|
|Leora Horn||Ph: 615-322-4967|
|Leora Horn||Principal Investigator|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas|
|Joan H. Schiller||Ph: 214-648-4180|
|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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