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H. Cheng



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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-102 - Phase I Study of Inhaled 5-Azacytidine in Patients with Advanced NSCLC (ID 546)

      09:30 - 09:30  |  Author(s): H. Cheng

      • Abstract
      • Slides

      Background:
      Epigenetic changes due to promoter hypermethylation have been shown to cause loss of tumor suppressor gene (TSG) function in NSCLC. Significant toxicity and lack of tumor selectivity have been the main limitations of systemic demethylating agents. We previously showed that aerosolized 5-Azacytidine (Aza) was superior to systemic administration in prolonging the survival of mice with carcinogen-induced lung cancer. These results suggest that inhaled Aza could inhibit lung cancer initiation and progression in subjects with chronic airborne carcinogen exposure. Thus, we designed the first phase I study of aerosolized Aza to determine the minimum effective dose of inhaled Aza required to induce relevant TSG re-expression in the bronchial epithelium of patients with advanced NSCLC.

      Methods:
      This is a phase I study following a 6+6 dose escalation and de-escalation design. Patients with advanced NSCLC, who have received at least one prior standard chemotherapy or targeted therapy, with ECOG PS 0-1, and adequate baseline bone marrow reserve, pulmonary reserve, and organ function are eligible. This study has received IRB and FDA approval as of 01/2015. Patients will be treated with inhaled Aza daily (20-minute inhalation) x 5 days per week once every 2 weeks. Based on our toxicity studies in mice, the recommended starting dose is 15 mg/m[2] . Dose escalation will proceed if <33% subjects in a given cohort experience pre-defined dose limiting toxicity (DLT) defined as grade 2 or higher pulmonary toxicity, grade 4 anemia, neutropenia, thrombocytopenia or any grade 3 or higher non-hematologic toxicity. The primary objective of the study is to determine the minimum effective dose of inhaled Aza required to induce re-expression of 5 relevant candidate TSGs (p16, H-Cad, OPCML, SFRP-1, and RASSF1A) that are silenced in the bronchial tissue of 20-50% heavy smokers with lung cancer. This will be determined in the bronchial epithelium of patients with advanced NSCLC in pre and post treatment biopsies. Secondary objectives include determining changes in global methylation patterns in the bronchial epithelium, and changes in methylation patterns in the exhaled breath. Clinical trial information: NCT02009436. Supported by NIH CA154755

      Results:
      not applicable

      Conclusion:
      not applicable

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