Inhaled drug combo aims to boost lung cancer treatment before surgery
NCT ID NCT06694454
First seen Jun 25, 2026 · Last updated Sep 21, 2026 · Updated 60 times
Summary
This study tests whether adding an inhaled form of the drug azacytidine to standard chemotherapy and immunotherapy (durvalumab) can improve outcomes for people with early-stage non-small cell lung cancer before they have surgery. The trial involves 60 adults with operable stage IB-IIIA NSCLC. Participants receive the inhaled drug for three days each cycle, plus IV chemo and immunotherapy, followed by tumor removal surgery. The goal is to find the safest and most effective dose and see if this combination can eliminate all cancer cells in the removed tissue.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- inhaled azacytidine (a drug that affects gene activity) combined with standard chemotherapy (carboplatin and paclitaxel) and durvalumab (an immunotherapy)
- What this could lead to
- If it works, this could lead to a new treatment option that helps shrink early-stage lung cancer before surgery, potentially reducing the chance of the cancer coming back.
- What could go wrong
- This is an early-phase trial with only 60 people, so the benefits are not proven yet. The inhaled drug is experimental for lung cancer, and side effects from the combination therapy could be significant.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 60 people
The number the study aims to enrol. It can still change while the study runs.
- Expected to start
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Sep 2026
An estimate. Start dates often move.
- Expected to finish
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Dec 2034
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 to 120 years
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
* INCLUSION CRITERIA: * 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. Women of childbearing potential should also avoid egg donation or storage from the time they give informed consent until at least 6 months after their last dose of durvalumab. Individuals able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 3 months after the last dose of the study drug(s). Note: participants who have cisplatin as part of SOC chemo must agree to use an effective method of contraception for 11 months. We also will recommend these individuals with partners of childbearing potential to ask partners to be on highly effective birth control (hormonal, intrauterine device (IUD), surgical sterilization). * 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 CRITERIA: * 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.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
1 site. The list below names each one and where it is.
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The official record
The full official record for this study. This one lists no contact details, but it is the first place any would appear.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
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