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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01886573
First received: June 21, 2013
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Stage IA Non-small Cell Lung Cancer
Stage IB Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Drug: azacitidine
Drug: entinostat
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: pharmacological study

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Genome-Wide Methylation and Gene Re-expression Analysis of Resectable Lung Tumor Tissue Pairs Obtained Pre- and Post-Treatment With 5-Azacytidine and Entinostat

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Change in aberrant genome-wide promoter methylation [ Time Frame: Baseline up to day 20 ] [ Designated as safety issue: No ]
    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.

  • Change in gene expression [ Time Frame: Baseline up to day 20 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 [ Time Frame: Up to 4 weeks after surgery ] [ Designated as safety issue: Yes ]
  • Reversibility of toxicities [ Time Frame: Up to 4 weeks after surgery ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: June 2013
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (azacitidine, entinostat)
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
Given SC
Other Names:
  • 5-AC
  • 5-azacytidine
  • azacytidine
  • Vidaza
Drug: entinostat
Given PO
Other Names:
  • HDAC inhibitor SNDX-275
  • SNDX-275
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To measure reversal of aberrant genome-wide promoter methylation and gene re-expression in paired, pre- and post- treatment lung tumor tissue pairs from patients with newly diagnosed, surgically resectable non-small cell lung cancer before and after exposure to a single neoadjuvant cycle of 5-azacytidine (azacitidine) and entinostat.

SECONDARY OBJECTIVES:

I. To measure the 3-year disease-free survival of operable non-small cell lung cancer (NSCLC) patients who receive 1 cycle of preoperative epigenetic treatment.

II. To determine any potential toxicities, and reversibility of toxicities, of a single pre-operative cycle of 5-azacytidine and entinostat.

OUTLINE:

Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (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).

After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years and then every 6 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Inclusion of women and minorities:

    • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01886573

Locations
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Dennie V. Jones    859-257-2014    dennie.jones@uky.edu   
Principal Investigator: Dennie V. Jones         
United States, New Mexico
University of New Mexico Recruiting
Albuquerque, New Mexico, United States, 87106
Contact: Montaser Shaheen    505-272-4946    moshaheen@salud.unm.edu   
Principal Investigator: Montaser Shaheen         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Joan H. Schiller    214-648-4180    joan.schiller@utsouthwestern.edu   
Principal Investigator: Joan H. Schiller         
Sponsors and Collaborators
Investigators
Principal Investigator: Montaser Shaheen University of New Mexico
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01886573     History of Changes
Other Study ID Numbers: NCI-2013-01186, NCI-2013-01186, CTEP 9431, INST 1117, 9431, R21CA161561, P30CA118100
Study First Received: June 21, 2013
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Azacitidine
Histone Deacetylase Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014