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

NCT ID: NCT02009436

Last Updated: 2020-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-09
• Study Completion Date: 2018-07-18

Brief Summary

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.

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.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Given via nebulizer

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

Azacitidine

Given via nebulizer

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; U-18496; Vidaza

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roman Perez-Soler

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

Albert Einstein College of Medicine

The Bronx, New York, United States

Countries

United States

References

Cheng H, Zou Y, Shah CD, Fan N, Bhagat TD, Gucalp R, Kim M, Verma A, Piperdi B, Spivack SD, Halmos B, Perez-Soler R. First-in-human study of inhaled Azacitidine in patients with advanced non-small cell lung cancer. Lung Cancer. 2021 Apr;154:99-104. doi: 10.1016/j.lungcan.2021.02.015. Epub 2021 Feb 17.

Reference Type: DERIVED

PMID: 33636454 (View on PubMed)

Other Identifiers

NCI-2014-01269

Identifier Type: REGISTRY

Identifier Source: secondary_id

2013-382

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA013330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2013-382

Identifier Type: -

Identifier Source: org_study_id