Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery

NCT ID: NCT01207726

Last Updated: 2019-02-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2013-05-31

Brief Summary

This study combines the deoxyribonucleic acid (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).

Detailed Description

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.

Conditions

Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Given SC

Entinostat

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Arm II (standard of care)

Patients receive standard of care.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Azacitidine

Given SC

Intervention Type: DRUG

Entinostat

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; U-18496; Vidaza; HDAC inhibitor SNDX-275; MS 27-275; MS-275; SNDX-275

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
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [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
• Human immunodeficiency virus (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Rudin

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Locations

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Anne Arundel Medical Center

Annapolis, Maryland, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

NCI-2012-02901

Identifier Type: REGISTRY

Identifier Source: secondary_id

NA_00038631

Identifier Type: -

Identifier Source: secondary_id

J1037

Identifier Type: OTHER

Identifier Source: secondary_id

8311

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02901

Identifier Type: -

Identifier Source: org_study_id