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)

Summary

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.

...

Conditions

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

Interventions

DRUG

azacytidine

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.

DRUG

carboplatin

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.

DRUG

paclitaxel

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.

DRUG

durvalumab

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.

DRUG

cisplatin

Cisplatin (IV), 75 mg/m\^2, administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.

DRUG

gemcitabine

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.

DRUG

pemetrexed

Pemetrexed (IV), 500 mg/m\^2, administered on day 4 of every cycle (1 cycle=21 days), for a maximum (total) of 3 cycles.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• David S Schrump, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-27

Primary Completion

2031-12-31

Completion

2034-12-31

FDA Drug

Yes

Countries

• United States

Study Locations