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)

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT06694454
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Carcinoma, Non-Small Cell Lung
  • Non Small Cell Lung Cancer
  • Non Small Cell Lung Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Non-small Cell Lung Cancer (NSCLC)

Eligibility Criteria

Sex
ALL
Age
18 Years - 120 Years
Healthy Volunteers
Not accepted

Interventions

  • azacytidine — DRUG
    Aerosolized azacytidine (AZA) via nebulizer on 3 consecutive days during the first week of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles. Azacytidine will be given at escalating doses in phase 1, and at the established RP2D in phase 2.
  • carboplatin — DRUG
    Carboplatin (intravenous/IV), area under the serum drug concentration-time curve (AUC)=5-6 mg/mL/min based on cancer histology administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.
  • paclitaxel — DRUG
    Paclitaxel (IV), 200 mg/m\^2, is administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.
  • durvalumab — DRUG
    Durvalumab (IV) administered as a flat dose of 1500 mg on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.
  • cisplatin — DRUG
    Cisplatin (IV), 75 mg/m\^2, administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.
  • gemcitabine — DRUG
    Gemcitabine (IV), 1,250 mg/m\^2, administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.
  • pemetrexed — DRUG
    Pemetrexed (IV), 500 mg/m\^2, administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.

Study Details

Background: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Surgery to remove the tumors is the standard treatment for people diagnosed with early stages of NSCLC. Despite complete removal of these tumors, many recur (happen again). An FDA-approved drug combination to treat early-stage NSCLC prior to the surgery is durvalumab plus standard chemotherapy. The FDA approved infusion drug azacytidine \[AZA\] is used to treat several diseases because it can rapidly kill dividing cells (including cancer cells) but it is not approved for NSCLC. An inhaled (aerosolized) form of AZA is also not approved for NSCLC. However, researchers want to know if an inhaled version of AZA can help improve treatment of people with NSCLC because inhaled AZA goes directly into the lungs with limited absorption into the bloodstream. Objective: To find the safest and most effective dose of inhaled AZA in participants with early-stage non-small cell lung cancer (NSCLC) that can still be removed by surgery. Eligibility: Adults aged 18 and older with operable early-stage NSCLC. Participants will be required to also enroll in NIH protocol 06C0014 which allows for pre- and post-treatment biopsies and bloodwork to be obtained for additional research studies. Design: Participants will be screened. They will have a physical exam with blood tests. Their medical records will be reviewed. They will have imaging scans and tests of their heart and lung functions. Participants will be required to have a tissue sample (biopsy) taken of their tumor prior to receiving study drug and again during surgery after Cycle 3; airway tissue biopsies and collection of collect bronchial (lung) fluid may also be done. Participants will receive the study treatment for 3 cycles. Each cycle is 21 days. They will need to come to the NIH Clinical Center (CC) on days 1-4 of Cycles 1-3. AZA will be given as a drug mist that can be inhaled (like the type of mist in an asthma inhaler) using a nebulizer at the NIH Clinical Center (CC) for 3 days in a row (consecutive days) during the first week of each cycle. The participant will inhale the AZA drug mist for 20 to 30 minutes each time. Participants will also receive durvalumab and a specific 2-drug assigned chemotherapy by intravenous (IV) infusion on day 4 of each cycle. Participants will have a follow-up visit 2 weeks after their last dose of study drugs. Then they will have planned surgery to remove the tumors. Participants will have additional follow-up visits at the NIH CC about 1 and 3 months after the surgery, and then for every 3 months for up to 3 years. ...

Key Dates

Start date
Jun 16, 2026
Status verified
Jun 2026
Primary completion
Dec 31, 2031
Completion
Dec 31, 2034

Study Design

Enrollment
60 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: 1/ Phase I Dose Escalation
    Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine
  • Experimental: 2/ Phase II Dose Expansion
    Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine

Primary Outcome Measure

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... [ Time Frame: starts at initiation of study drug, though end of DLT period ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
NCI Referral Office
[email protected]
1-888-NCI-1937

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