Study of durvalumab or placebo administered with radiation therapy for patients with early stage non-small cell lung cancerStudy of osimertinib administered after radiation therapy in patients with early stage non-small cell lung cancer harboring an EGFR mutatio

Phase 1

• Conditions: Main cohort: Patients with unresected Stage I/II, lymph-node negative Non-small Cell Lung CancerOsimertinib cohort, Open-label, Single arm for patients with unresected stage I/II, lymph done negative NSCLC harboring a sensitizing EGFR mutation; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 21.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-002572-41-NL
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-15
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 690

Inclusion Criteria

Applicable to both cohorts:
1. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling and analyses
2. Age =18 years
3. Histologically or cytologically documented Stage I to II NSCLC, with clinical T1 to T3N0M0 Stage I/II disease and planned to receive definitive treatment with SBRT (Stereotactic Body Radiation Therapy). Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy
4. Planned SoC SBRT as definitive treatment
5. World Health Organization (WHO)/ECOG PS of 0, 1, or 2
6. Patients with central or peripheral lesions are eligible
7. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
8. Staging studies must be done during screening (PET-CT within 10 weeks)
9. Submission of available tumor tissue or cell block samples from FNA

Main cohort (durvalumab) specific:
1. Life expectancy of at least 12 weeks
2. Body weight >30 kg
3. Adequate organ and marrow function required
4. Pulmonary Function Testing within 16 weeks of randomization

Osimertinib cohort specific:
1. Confirmation by local laboratory that the tumor harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
2. Adequate bone marrow reserve or organ function required
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 590

Exclusion Criteria

Applicable to both cohorts:
1. Mixed small cell and non-small cell cancer
2. History of another primary malignancy with exceptions

Main cohort specific:
1. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
2. History of allogeneic organ transplantation
3. History of active primary immunodeficiency or autoimmune disorders
4. History of non-infectious pneumonitis requiring steroids
5. Active infection including tuberculosis, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
6. Prior exposure to immune-mediate therapy

Osimertinib cohort specific:
1. Patients currently receiving potent inducers of CYP3A4
2. Patients with known or increased risk factor for QTc prolongation
3. Treatment with any of the following:
-Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation
-Prior treatment with neoadjuvant or adjuvant EGFR TKI
-Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4
-Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
4. Any of the following cardiac criteria
-Mean resting corrected QT interval >470 msec, obtained from 3 ECGs
-Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
-Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained -sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval
-Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified