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)

Launched by NATIONAL CANCER INSTITUTE (NCI) · Nov 18, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for early-stage non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Researchers want to see if inhaling a drug called azacytidine, combined with standard chemotherapy and another drug called durvalumab, can help improve outcomes for patients before they have surgery to remove their tumors. The goal is to find the safest and most effective dose of the inhaled drug that can help in treating this type of cancer.

To participate in this trial, you must be an adult (18 years or older) with operable early-stage NSCLC that can be surgically removed. You should not have received any previous treatment for your lung cancer, and you will need to undergo some tests to ensure you are healthy enough for the study. If you join, you will receive the inhaled medication along with chemotherapy for three treatment cycles, each lasting 21 days, followed by surgery to remove your tumor. There will also be follow-up visits after your surgery to monitor your health. This trial is not yet recruiting participants, so you may want to check back for updates if you are interested.

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ALL

Eligibility criteria

• * 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.
• • 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.