Azacitidine in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer

February 5, 2020 updated by: Albert Einstein College of Medicine

Phase I Study of Inhaled Vidaza® in Patients With Advanced NSCLC

This pilot phase I trial studies the side effects and best dose of azacitidine in treating patients with lung cancer that is stage IV or has returned after previous treatments (recurrent). Azacitidine is a drug used in chemotherapy that may stop tumor cells from growing or spreading by activating genes that help prevent cancer growth, called tumor suppressor genes. As people age, these genes are silenced by a chemical reaction that occurs naturally in the body, or by exposure to environmental factors such as smoking. Azacitidine may help reverse this process and restore the function of the tumor suppressor genes. Delivering azacitidine directly into the lungs by inhalation may work better in treating lung cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and toxicity of inhaled Vidaza® (azacitidine) with special emphasis on pulmonary toxicity.

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetics of inhaled Vidaza®. II. To determine the changes in global methylation patterns in the bronchial epithelium (bronchial tissue samples) pre and post treatment.

III. To determine the changes in methylation patterns in the exhaled breath. IV. To evaluate the efficacy of inhaled Vidaza® on intra-thoracic tumors (response rate by Response Evaluation Criteria in Solid Tumors [RECIST] criteria for intrapulmonary lesions).

V. To estimate the progression free, intra-thoracic tumor progression free and overall survival.

VI. To determine the minimum effective dose of inhaled Vidaza® required to induce changes in the methylation status and re-expression of a panel of genes, including 5 candidate tumor suppressor genes (cyclin-dependent kinase inhibitor 2A [p16], h-cadherin [H-Cad], opioid binding protein/cell adhesion molecule-like [OPCML], secreted frizzled-related protein 1 [SFRP-1], and ras association domain family 1 [RASSF1A]) that are silenced in 20-50% of bronchial tissue of heavy smokers with lung cancer.

OUTLINE: This is a dose-escalation study.

Patients receive azacitidine via nebulizer over 20 minutes once daily (QD) on days 1-5 and 15-19. Treatment repeats every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients may continue treatment on a case-by-case basis at the discretion of principal investigator and Institutional Review Board.

After completion of study treatment, patients are followed up at 4-6 weeks and then every 3 months thereafter.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically proven (either histologic or cytologic) diagnosis of stage IV or recurrent non-small cell lung cancer (according to American Joint Committee on Cancer [AJCC] staging, 7th edition)
  • Patient has received at least one prior standard chemotherapy or targeted therapy for treatment of lung cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,500 cells/ul
  • Platelets >= 100,000 cells/ul
  • Hemoglobin >= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= g/dl is acceptable)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN)
  • Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x the ULN
  • Adequate pulmonary reserve defined as adequate airflow defined by a measured forced expiratory volume (FEV1) not less than 50% of the predicted value and adequate pulmonary reserve as evidenced by a FEV1/forced vital capacity (FVC) ratio of 65% or greater
  • Patient must sign study specific informed consent prior to study entry

  • Women of childbearing potential must have:

    • A negative serum or urine pregnancy test (sensitivity =< 25 IU human chorionic gonadotropin [HCG]/L) within 72 hours prior to the start of study drug administration
    • Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy

Exclusion Criteria:

  • Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study
  • Contraindication to or unwillingness to undergo study related procedures including a repeat bronchoscopy
  • Participation in an investigational drug or device study or treatment with any antineoplastic agent within 14 days of the first day of dosing on this study

  • History of significant bleeding disorder unrelated to cancer, including:

    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
    • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • History of hypersensitivity to mannitol
  • Unwillingness or inability to comply with the study protocol for any other reason

  • Women who:

    • Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or
    • Have a positive pregnancy test at baseline, or
    • Are pregnant or breastfeeding
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Treatment (azacitidine)
Patients receive azacitidine via nebulizer over 20 minutes QD on days 1-5 and 15-19. Treatment repeats every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients may continue treatment on a case-by-case basis at the discretion of principal investigator and Institutional Review Board.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Azacitidine
Given via nebulizer
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Minimum effective dose of inhaled azacitidine, defined as the dose required to induce the re-expression of any of the relevant 5 candidate tumor suppressor genes by two fold between pre and post treatment bronchial biopsies in 50% of evaluable patients
Time Frame: Up to day 28 after the first course of treatment
The data will be analyzed and presented in descriptive fashion.
Up to day 28 after the first course of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Albert Einstein College of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 9, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 18, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 18, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 21, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 12, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2013-382 (OTHER: Albert Einstein College of Medicine)
  • P30CA013330 (U.S. NIH Grant/Contract)
  • NCI-2014-01269 (REGISTRY: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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