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)
- Conditions
- Interventions
- Registration Number
- NCT06694454
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
...
- Detailed Description
Background:
* Lung cancer is the leading cause of cancer-related mortality worldwide and accounted for nearly 160,000 deaths in 2023 in the US.
...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 1/ Phase I Dose Escalation azacytidine Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 1/ Phase I Dose Escalation carboplatin Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 1/ Phase I Dose Escalation paclitaxel Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 1/ Phase I Dose Escalation durvalumab Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 1/ Phase I Dose Escalation cisplatin Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 1/ Phase I Dose Escalation gemcitabine Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 1/ Phase I Dose Escalation pemetrexed Histology specific SOC platinum-based chemotherapy with durvalumab plus escalating/de-escalating doses of aerosolized azacytidine 2/ Phase II Dose Expansion azacytidine Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine 2/ Phase II Dose Expansion carboplatin Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine 2/ Phase II Dose Expansion paclitaxel Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine 2/ Phase II Dose Expansion durvalumab Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine 2/ Phase II Dose Expansion cisplatin Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine 2/ Phase II Dose Expansion gemcitabine Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine 2/ Phase II Dose Expansion pemetrexed Histology specific SOC platinum-based chemotherapy with durvalumab plus RP2D of aerosolized azacytidine
- Primary Outcome Measures
Name Time Method 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 NSCLC baseline (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.
- Secondary Outcome Measures
Name Time Method To evaluate pharmacokinetics All participants: Cycle 1, Day 1 or 2, and Cycle 3, Day 1 or 2. Participants with MTD treatment: Cycle 1, Day 1 or 2, and Cycle 2, Day 1 or 2, and Cycle 3, Day 1 or 2. Pharmacokinetic endpoints will be reported using descriptive statistics.
To evaluate safety of the combination of AZA and chemo-durvalumab in participants with operable early-stage NSCLC starts at initiation of study drug, through 64 days after the last study drug administration Safety of the agents will be assessed by determining the grade of adverse events noted in each participant and reporting the fraction with Grade 3 and Grade 4 adverse events. Safety data will be presented in a summary. The safety data will consist of the reporting of all adverse events, and may also include reporting vital signs, physical examination data, a...
To evaluate event-free survival (EFS) baseline, Day 64 (treatment evaluation), then post-surgical 1 month, 3 months, and every 3 months thereafter until disease progression, until up to 3 years from the treatment initiation Event-free survival (EFS) at three years post treatment will be determined as the duration of time from start of treatment to time of disease recurrence or appearance of new primary cancer, whichever occurs first as appropriate using the Kaplan-Meier method and reported along with a 95% confidence interval, separately for phase I and II. The median EFS will ...
To evaluate objective response (complete response [CR] + partial response [PR]) and stable disease [SD] per RECIST 1.1 baseline, and at Day 64 (treatment evaluation) The objective response rate will be based on CR+PR and the disease stabilization rate (SD) and reported separately in phase I and II along with a 95% confidence interval for each.
To evaluate major pathologic response (MPR) rate baseline (pre-treatment biopsy), and at the time of SOC surgery post-cycle 3 MPR rate is defined as \<10% viable cancer cells in samples collected per histopathologic assessment. The objective response rate based on the MPR rate will be reported separately in phase I and II along with a 95% confidence interval for each.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States