AZA-AEGEAN: Inhaled Azacytidine for Early-Stage Lung Cancer
This study is for people with early-stage non-small cell lung cancer (NSCLC) that can be removed by surgery. It combines an inhaled form of azacytidine with standard chemotherapy (carboplatin/paclitaxel or cisplatin) and durvalumab before surgery. Researchers want to find the safest dose of inhaled azacytidine (Phase 1) and then see how many people have a complete disappearance of cancer cells in their removed tumor (pathologic complete response) when using this combination (Phase 2). You can join if you are 18 to 120 years old and have resectable stage IB-IIIA NSCLC. The study aims to enroll 60 participants.
- Study design
- This is an interventional study with a planned enrollment of 60 participants. It has a Phase 1 part to find the best dose and a Phase 2 part to measure treatment success.
- What's involved
- You would receive azacytidine, chemotherapy (carboplatin/paclitaxel or cisplatin), and durvalumab for a maximum of 3 cycles before surgery. Biopsies will be taken before treatment and at the time of surgery.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study measures outcomes at the end of the dose-limiting toxicity period (Phase 1) and at baseline and after surgery (Phase 2).
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06694454
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)
Suspended
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~60 participants
Updated 2026-08-31 on ClinicalTrials.gov
What's tested:azacytidinecarboplatinpaclitaxeldurvalumabcisplatingemcitabine
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase I: To determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of neoadjuvant aerosolized AZA in participants with operable early-stage NSCLC treated with standard of care (SOC) platinum-based chemotherapy and du...
Measured over starts at initiation of study drug, though end of DLT period
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- David S Schrump, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Histologically or cytologically confirmed, resectable per standard of care stage IB-IIIA non-small cell lung cancer (NSCLC) irrespective of programmed death-ligand 1 (PD-L1) expression. Note: Confirmation is required by NCI Laboratory of Pathology (LP).
Willingness to undergo tumor resection surgery per standard of care (SOC) guidelines following induction therapy (platinum chemotherapy and durvalumab).
Participants must have disease that can be safely accessed via bronchoscopic, thoracoscopic, or percutaneous biopsy techniques, and be willing to undergo tumor biopsy before treatment.
No prior therapy for the NSCLC.
Measurable disease per RECIST 1.1
Age \>= 18 years.
Body weight \> 30kg.
ECOG Performance Status \<= 1
Participants must have adequate pulmonary reserve evidenced by predicted post-op FEV1 and adjusted DLCO \>= 40% at screening.
Participants must have pCO2 \<= 45 and pO2 \>=60 on room air by arterial blood gas (ABG) if O2 sat by pulse oximetry is\<= 92% on room air at screening.
Adequate organ and marrow function as defined below:
Leukocytes \>3,000/microL
Absolute neutrophil count \>1,500/microL (without transfusion or cytokine support)
Absolute lymphocyte count \> 800/microL
Platelets \>100,000/microL
Hemoglobin \>= 9.0 g/dL
Prothrombin time (PT) no more than 2 seconds above the upper limit of normal (ULN)
Total bilirubin OR Direct bilirubin \< 1.5 X institutional upper limit of normal OR \<= ULN for participants with total bilirubin \>= 1.5 ULN
Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \< 2.5 X institutional ULN
Serum albumin \>= 2.0 mg/dL
Creatinine OR Creatinine clearance (eGFR) \<= 1.6 mg/ml OR \>60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal
Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization, abstinence) for the duration of the study treatment and up to 6 months after the last dose of the study drug(s). Note: participants who have cisplatin as part of SOC chemo must agree to use a highly effective method of contraception for 14 months.
Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after the last dose of the study drug(s).
Participants with history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness are included if on appropriate antiretroviral therapy with HIV viral load \<400 copies/mL.
Participants must agree to not donate blood from the study entry and up to 3 months after the last dose of the study drug(s).
Participants must be co-enrolled in protocol 06C0014: Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies .
The ability of a participant to understand and the willingness to sign a written informed consent document.
Exclusion
Medically inoperable because of clinical co-morbidities.
Participants with T4 tumors invading the diaphragm, mediastinum, carina, trachea, esophagus, heart, great vessels, recurrent laryngeal nerve, or vertebral body.
Participants who experienced serious immune adverse events that required discontinuation of immune checkpoint inhibitor therapy for a prior non-NSCLC malignancy.
History of known EGFR or ALK alterations in the tumor.
History of active autoimmune disease including colitis, nephritis, hypophysitis, or neuropathy, with the exceptions of:
Diabetes type I, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment.
History of pneumonitis or interstitial lung disease.
Clinically significant cardiovascular/cerebrovascular disease as follows:
cerebral vascular accident/stroke (within 6 months prior to study treatment initiation)
myocardial infarction (within 6 months prior to study treatment initiation)
unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II, https://manual.jointcommission.org/releases/TJC2016A/DataElem0439.html#:\~:text=Class%20II%20%2D%20Mild%20symptoms%20(mild,Class%20IV%20%2D%20Severe%20limitations), serious cardiac arrhythmia, clinically significant bleeding or clinically significant pulmonary embolism at screening.
Active Hepatitis A (HAV), Hepatitis B (HBV) (HbsAg reactive), or Hepatitis C (HCV) (HCV RNA \[qualitative\] is detected) at screening.
Other active infections requiring systemic therapy at screening.
Positive beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening.
Systemic corticosteroids at doses above physiologic levels (\> 10 mg of prednisone or equivalent per day), or inhaled corticosteroids within 14 days before study treatment initiation. Administration of steroids through a route known to result in a minimal systemic exposure (i.e., topical, intro-ocular, or intra-articular) is allowed.
Major surgical procedure within 28 days prior to the study treatment initiation. Note: Local surgery of isolated lesions for palliative intent is acceptable provided other site(s) of disease is available for response assessment.
History of allogenic organ transplantation.
History of another primary malignancy except for malignancy treated with curative intent and with no known active disease \>= 5 years before the study treatment initiation.
Administration of live attenuated vaccines within 30 days prior to study treatment initiation. Note: Administration of inactivated vaccines (e.g., inactivated influenza vaccines) is permitted before or during the study.
Administration of investigational drug on other clinical trial within 14 days prior to study treatment initiation.
History of hypersensitivity to Mannitol.
Herbal and natural remedies that may have immune-modulating effects within 7 days prior to study treatment initiation.
Uncontrolled intercurrent illness evaluated by history and physical exam or situation that would limit compliance with study requirements.
What this trial measures
- Phase I: To determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of neoadjuvant aerosolized AZA in participants with operable early-stage NSCLC treated with standard of care (SOC) platinum-based chemotherapy and du...starts at initiation of study drug, though end of DLT period
DLTs noted at each dose level will be reported.
- Phase II: To determine the frequency of pathologic complete responses (pCR) in participants receiving aerosolized AZA, durvalumab, and SOC platinum-based chemotherapy as induction therapy for early-stage NSCLCbaseline (pre-treatment biopsy), and at the time of SOC surgery post-cycle 3
Pathologic complete responses (pCR) is defined as no viable cancer cells in samples collected on histopathologic assessment. Fraction of evaluable participants who experience a pCR will be determined and reported along with 80% and 95% two-sided confidence intervals.