Azacitidine and Entinostat in Treating Patients With Newly Diagnosed Stage IA-IIIA Non-Small Lung Cancer Undergoing Surgery

NCT01886573 | Terminated Phase 1

• 6 other identifiers: NCI-2013-01186CTEP 9431INST 11179431P30CA118100R21CA161561
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

This pilot clinical trials studies azacitidine and entinostat in treating patients with newly diagnosed stage IA-IIIIA non-small cell lung undergoing surgery. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of cancer tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with entinostat may be an effective treatment for non-small cell lung cancer.

Conditions

Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Change in aberrant genome-wide promoter methylation

  Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes \[e.g., PRC2\]) and pathways affected.

  Baseline up to day 20

• Change in gene expression

  Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes \[e.g., PRC2\]) and pathways affected.

  Baseline up to day 20

Secondary Outcomes (3)

• Disease-free survival

  Up to 3 years

• Reversibility of toxicities

  Up to 4 weeks after surgery

• Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02

  Up to 4 weeks after surgery

Study Arms (1)

Treatment (azacitidine, entinostat)

EXPERIMENTAL

Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Patients undergo surgery between days 11-20 (this period can be extended 10 more days if adverse events from therapy impose a surgical risk).

Drug: Azacitidine; Drug: Entinostat; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Interventions

Azacitidine DRUG

Given SC

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

Treatment (azacitidine, entinostat)

Entinostat DRUG

Given PO

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

Treatment (azacitidine, entinostat)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (azacitidine, entinostat)

Pharmacological Study OTHER

Correlative studies

Treatment (azacitidine, entinostat)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (azacitidine, entinostat)

Eligibility Criteria

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

You may qualify if:

• Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or bronchoscopic for suspected diagnosis of NSCLC
• Able to understand and sign an informed consent discussing the risks and benefits of obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy available secondary to institutional tissue collection protocols may substitute such a biopsy for the study-required pre-treatment biopsy
• Histologically confirmed diagnosis of operable NSCLC that has not been previously treated
• Clinical stage IA-IIIA
• Appropriate candidate for surgical management, in the opinion of the treating thoracic surgeon
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 at the time of initiation of neoadjuvant epigenetic therapy
• Absolute neutrophil count \> 1,000/mcL
• Platelets \> 100,000/mcL
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x institutional ULN
• Creatinine \< 1.5 x institutional ULN
• Able to understand and sign an informed consent
• 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
• Both men and women and members of all races and ethnic groups are eligible for this trial; the coordinating center will be responsible for ensuring each participating site is accruing a representative sample consistent with the estimate of population representation in the site's geographical location for race and ethnic groups as determined by the Census Bureau to assure overall target goals are met

You may not qualify if:

• Patients who have received prior chemotherapy or radiation for their diagnosis of lung cancer
• Patients may not be receiving any other investigational agent
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or 5-azacytidine
• 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; breastfeeding should be discontinued if the mother is treated on this protocol
• Any co-morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
• Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible
• Known or suspected hypersensitivity to azacitidine or mannitol
• Patients with advanced malignant hepatic tumors
• Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study; Note: study participants with stage II or III NSCLC, or stage I NSCLC with tumor size greater than 4 cm, should be offered standard adjuvant platinum-based chemotherapy in accordance with local practice (post-operatively)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, 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

Study Officials

• Montaser Shaheen

  University of New Mexico

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2013
• First Posted: June 26, 2013
• Study Start: June 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: November 18, 2016

Record last verified: 2016-11

Locations

US (3)