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

NCT01207726 | Terminated Phase 2 Results

• 5 other identifiers: NCI-2012-02901NA_00038631J10378311P30CA006973
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 9

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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%.

  3 years

Secondary Outcomes (6)

• Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform

  Up to 2 years

• Median Disease-free Survival

  Up to 5 years

• Number of Relapses and Deaths Per Total Time of Follow-up Comparing Patients With N2 Lymph Nodes in Terms of Methylated and Unmethylated

  Up to 5 years

• Overall Survival

  Up to 5 years

• Presence of Methylation Patterns

  Up to 2 years

Study Arms (2)

Arm I (azacitidine, entinostat)

EXPERIMENTAL

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.

Drug: Azacitidine; Drug: Entinostat; Other: Laboratory Biomarker Analysis

Arm II (standard of care)

NO INTERVENTION

Patients receive standard of care.

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm I (azacitidine, entinostat)

Entinostat DRUG

Given PO

Also known as: HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275

Arm I (azacitidine, entinostat)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (azacitidine, entinostat)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Azacitidine; entinostat

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Charlie Rudin, MD
• Organization: SKCCC

rudinc@mskcc.org

646.888.4527

Study Officials

• Charles Rudin

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2010
• First Posted: September 23, 2010
• Study Start: September 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: February 5, 2019
• Results First Posted: February 5, 2019

Record last verified: 2019-01

Locations

US (9)