Actively Recruiting
Phase I/II Study of Neoadjuvant Inhaled Azacytidine With Platinum-Based Chemotherapy and Durvalumab for Operable Early-Stage Non-Small Cell Lung Cancer
Led by National Cancer Institute (NCI) · Updated on 2026-06-08
60
Participants Needed
1
Research Sites
156 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying early-stage non-small cell lung cancer (NSCLC), the most common type of lung cancer and a leading cause of cancer death worldwide. This trial aims to find the safest and most effective dose of inhaled azacytidine (AZA), a drug not yet approved for NSCLC, given before surgery along with standard chemotherapy and durvalumab. The study explores whether inhaled AZA, which delivers the drug directly to the lungs, can improve treatment outcomes by targeting cancer cells and their environment. Participants will receive up to three cycles of treatment, each lasting 21 days. Inhaled AZA will be given as a mist using a nebulizer for three consecutive days at the start of each cycle. On the fourth day, participants receive durvalumab and platinum-based chemotherapy drugs intravenously, with doses adjusted based on cancer type. After completing treatment cycles, participants will have surgery to remove tumors, followed by regular follow-up visits for up to three years. During the study, participants will undergo physical exams, blood tests, imaging scans, lung and heart function tests, and biopsies before and after treatment. Researchers will monitor safety, drug effects, tumor response, and survival outcomes. They will also collect tissue and fluid samples to study genetic and immune changes. Follow-up visits occur at two weeks post-treatment, then one and three months after surgery, and every three months thereafter, tracking health for up to three years.
CONDITIONS
Brief Title
Neoadjuvant Inhaled Azacytidine With Platinum-Based Chemotherapy and Durvalumab (MEDI4736) - a Combined Epigenetic-Immunotherapy (AZA-AEGEAN) Regimen for Operable Early-Stage Non-Small Cell Lung Cancer (NSCLC)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed resectable stage IB-IIIA non-small cell lung cancer (NSCLC)
- Willingness to undergo tumor resection surgery following induction therapy
- Disease accessible for biopsy and willingness to undergo tumor biopsy before treatment
- No prior therapy for NSCLC
- Measurable disease per RECIST 1.1
- Age 18 years or older
- Body weight greater than 30 kg
- ECOG performance status of 0 or 1
- Adequate pulmonary reserve with predicted post-operative FEV1 and adjusted DLCO at or above 40%
- pCO2 at or below 45 and pO2 at or above 60 on room air if oxygen saturation is 92% or below
- Adequate organ and marrow function as defined by specific blood count and chemistry levels
- Agreement to use effective contraception during treatment and for specified periods after last dose
- Willingness to discontinue breastfeeding during treatment and for 3 months after last dose
- Participants with controlled HIV infection on antiretroviral therapy with viral load below 400 copies/mL
- Agreement not to donate blood during study and for 3 months after last dose
- Co-enrollment in protocol 06C0014
- Ability to understand and sign informed consent
You will not qualify if you...
- Medically inoperable due to clinical co-morbidities
- Tumors invading major structures like diaphragm, mediastinum, carina, trachea, esophagus, heart, great vessels, recurrent laryngeal nerve, or vertebral body
- Previous serious immune adverse events requiring stopping immune checkpoint inhibitors for prior cancers
- History of EGFR or ALK alterations in tumor
- Active autoimmune diseases requiring immunosuppressive treatment, except certain controlled conditions
- History of pneumonitis or interstitial lung disease
- Significant cardiovascular or cerebrovascular disease within 6 months before treatment
- Active hepatitis A, B, or C infections at screening
- Other active infections needing systemic therapy at screening
- Positive pregnancy test in females of childbearing potential
- Use of systemic corticosteroids above physiologic doses or inhaled corticosteroids within 14 days before treatment
- Major surgery within 28 days before treatment, except certain palliative surgeries
- History of allogenic organ transplantation
- Another primary cancer within past 5 years except certain curatively treated malignancies
- Live attenuated vaccine administration within 30 days before treatment
- Use of investigational drugs within 14 days before treatment
- Known hypersensitivity to Mannitol
- Use of herbal or natural immune-modulating remedies within 7 days before treatment
- Uncontrolled illness or conditions that limit compliance with study requirements
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 9 weeks (3 cycles of 21 days each)
Participants receive neoadjuvant inhaled azacytidine on three consecutive days followed by platinum-based chemotherapy and durvalumab on day 4 of each 21-day cycle, repeated for up to 3 cycles.
3 treatment cycles with dosing on days 1 to 4 of each cycle
Duration - Within 3 weeks after treatment completion
Participants undergo tumor resection surgery within 3 weeks following completion of neoadjuvant therapy.
1 surgical visit
Duration - Up to 3 years
Participants are monitored for safety, event-free survival, and treatment outcomes after surgery, including evaluations at 1 month, 3 months, and every 3 months thereafter for up to 3 years from treatment initiation.
Visits at 1 month, 3 months, and every 3 months post-surgery
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
R
Rebecca B Alexander
D
David S Schrump, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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