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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2015-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Given SC

Entinostat

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Interventions

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Azacitidine

Given SC

Intervention Type DRUG

Entinostat

Given PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Other Intervention Names

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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

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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)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Montaser Shaheen

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico

Locations

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University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Countries

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United States