A Phase 2 interventional study of Osimertinib and Stereotactic Radiosurgery in Non-Small Cell Lung Cancer, Brain Metastases From Non-small Cell Lung Cancer (NSCLC) and EGFR Activating Mutation, sponsored by Cho Ray Hospital. Recruiting at 1 site in Vietnam. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by Cho Ray Hospital · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to learn whether adding stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT), delivered on a linear accelerator (LINAC), to osimertinib improves control of brain metastases in adults with stage IV non-small cell lung cancer (NSCLC) carrying a sensitizing EGFR mutation (exon 19 deletion or exon 21 L858R) whose brain metastases cause neurological symptoms (present at diagnosis or arising during osimertinib treatment). The main questions it aims to answer are:
Participants will:
BACKGROUND Brain metastases develop in 44-63% of patients with EGFR-mutant non-small cell lung cancer (NSCLC) during the course of disease and are associated with neurological morbidity and reduced quality of life. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with good central nervous system penetration, is the standard first-line treatment based on the FLAURA trial. However, among osimertinib-treated patients who do not receive local brain therapy, the brain is frequently the first site of progression, and intracranial relapse often arises from initially involved or residual lesions. Retrospective series suggest that adding upfront stereotactic radiation to EGFR-TKI improves intracranial and overall outcomes, and a pooled analysis of two randomized phase II trials (OUTRUN/TROG 17.02 and LUOSICNS) has reported encouraging results; prospective data remain limited, particularly in Southeast Asia. In Vietnam, Gamma Knife is available at few centres whereas LINAC is widely available. No prospective study has reported outcomes of osimertinib combined with LINAC-based SRS/SRT in Vietnamese patients.
OBJECTIVES
(1) To evaluate intracranial (RANO-BM) and extracranial (RECIST 1.1) response to osimertinib combined with LINAC-based SRS/SRT in EGFR-mutant NSCLC with brain metastases. (2) To evaluate survival outcomes (intracranial progression-free survival, progression-free survival, overall survival) and adverse events.
DESIGN Prospective, single-centre, single-arm, open-label interventional study conducted at the Department of Medical and Radiation Oncology, Oncology Center, Cho Ray Hospital, Ho Chi Minh City, Vietnam. The study population is patients with symptomatic brain metastases, i.e., brain metastases accompanied by neurological symptoms, either at diagnosis or arising while on osimertinib; symptoms are classified as raised intracranial pressure (headache, nausea/vomiting), focal neurological deficits (limb weakness, sensory disturbance, visual or language disturbance, seizure, imbalance) or cognitive-behavioural changes (memory/concentration decline, personality or mood change). Eligible patients are identified consecutively through the multidisciplinary oncology tumour board and enrolled after written informed consent. Time zero for all time-to-event endpoints is the first day of SRS/SRT.
INTERVENTION Systemic therapy: osimertinib 80 mg orally once daily. Patients not yet on systemic therapy start osimertinib concurrently with SRS/SRT; patients already receiving osimertinib continue it without interruption during SRS/SRT. Osimertinib is continued until progression, unacceptable toxicity or withdrawal; treatment after progression follows institutional practice.
Stereotactic radiation: frameless immobilization with a thermoplastic mask (Fraxion stereotactic system); CT simulation with slice thickness of 1 mm or less (Siemens Somatom Definition AS) fused with contrast-enhanced MRI (or PET); planning on Monaco TPS (VMAT/DCAT, flattening-filter-free beams); delivery on an Elekta Versa HD LINAC with cone-beam CT image guidance. GTV = contrast-enhancing lesion; CTV = GTV; PTV = GTV + 0-2 mm. Dose: lesions of 2 cm or smaller, 18 Gy in 1 fraction; lesions larger than 2 cm, 27 Gy in 3 fractions or 30 Gy in 5 fractions. Planning goals: GTV D100% at least 100% and Dmax at most 135% of prescription; PTV D98% at least 100%; Paddick conformity index close to 1; gradient index approximately 3-5. Normal-tissue constraints (1/3/5 fractions): normal brain V12 \< 5-10 cc / V20 \< 20 cc / V24 \< 20 cc; brainstem Dmax 8-12 / 21-24 / 25-30 Gy; optic nerves/chiasm Dmax 8-10 / 15-18 / 25-30 Gy. Planning is completed within 3 days of simulation and treatment is delivered within approximately 1 week.
ASSESSMENTS Baseline: history and examination, ECOG performance status, neurological symptoms, contrast-enhanced chest-abdomen CT (PET-CT or bone scan as indicated), contrast-enhanced brain MRI (CT if MRI is contraindicated), AJCC 8th edition TNM staging, complete blood count, liver and renal function, electrolytes, hepatitis B and C serology, ECG and echocardiography. Response: brain MRI (RANO-BM) and chest-abdomen CT (RECIST 1.1) every 12 weeks (3 osimertinib cycles) or when clinically indicated; images are reviewed by radiologists not involved in treatment. Safety (CTCAE v5.0): acute radiation toxicity recorded at each fraction by radiation therapists and physicians; clinic visits every 4 weeks; blood tests, ECG and echocardiography every 12 weeks; late radiation toxicity (radiation necrosis, intracranial haemorrhage, seizure) recorded throughout follow-up. After progression, participants are followed for subsequent therapy, intracranial progression (if extracranial progression occurred first), survival and late toxicity through clinic visits and telephone contact.
SAMPLE SIZE Sample size was calculated with the single-proportion formula n = Z\^2 p(1-p)/d\^2, with Z = 1.96 (95% confidence), an expected 6-month intracranial PFS rate p = 0.88 (based on OUTRUN/TROG 17.02) and precision d = 0.10, giving a minimum of 41 participants.
STATISTICAL ANALYSIS Continuous variables are summarized as mean (SD) or median (IQR); categorical variables as counts and percentages, compared with the chi-square or Fisher exact test. Response rates are reported with 95% confidence intervals. Time-to-event endpoints are estimated with the Kaplan-Meier method and compared with the log-rank test; multivariable Cox regression is used to explore factors associated with intracranial PFS and PFS (e.g., EGFR mutation subtype, number and size of brain metastases, T and N status). Two-sided p \< 0.05 is considered significant. Analyses are performed in Stata.
ETHICS The protocol was approved by the Ethics Committee in Biomedical Research, Cho Ray Hospital (approval No. 46-26/CN-HDDD, 27 February 2026; full-board review). All participants provide written informed consent; personal data are coded and kept confidential. The study forms part of a doctoral thesis at Hanoi Medical University.
7,620 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,838 are open to participants now.
This study's planned enrollment of 41 is below the median of 62 across 6,019 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Cho Ray Hospital is the lead sponsor of 5 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Osimertinib 80 mg orally once daily, started concurrently with or continued during SRS/SRT and continued until disease progression, unacceptable toxicity or withdrawal, plus LINAC-based stereotactic radiation to all brain metastases: 18 Gy in 1 fraction for lesions 2 cm or smaller; 27 Gy in 3 fractions or 30 Gy in 5 fractions for lesions larger than 2 cm.
Drug: Osimertinib · Radiation: Stereotactic Radiosurgery
Intervention 1 - Drug: Osimertinib Third-generation EGFR tyrosine kinase inhibitor, 80 mg orally once daily, swallowed whole at a fixed time each day with or without food. Started concurrently with SRS/SRT in treatment-naive patients or continued without interruption in patients already receiving it; continued until disease progression, unacceptable toxicity or withdrawal.
Also known as: Tagrisso; AZD9291
Intervention 2 - Radiation: Stereotactic Radiosurgery / Stereotactic Radiotherapy (LINAC) Frameless thermoplastic-mask immobilization, CT simulation (1 mm or less) fused with contrast-enhanced MRI, VMAT/DCAT planning with flattening-filter-free beams on Monaco TPS, delivery on an Elekta Versa HD with cone-beam CT guidance. PTV = GTV + 0-2 mm. 18 Gy/1 fraction (lesions 2 cm or smaller); 27 Gy/3 fractions or 30 Gy/5 fractions (lesions larger than 2 cm). Delivered within approximately 1 week of simulation.
Also known as: SRS, SRT, fractionated stereotactic radiotherapy
Intracranial objective response rate (iORR)
Percentage of participants with a best intracranial response of complete response (iCR) or partial response (iPR) according to RANO-BM on contrast-enhanced brain MRI (contrast-enhanced CT if MRI is not feasible). iCR: disappearance of all intracranial target and non-target lesions, no new lesions, no corticosteroids, clinically stable or improved. iPR: at least 30% decrease in the sum of longest diameters of target lesions (10 mm or larger) versus baseline, no new lesions, stable or decreased corticosteroids, clinically stable or improved.
Time frame: Assessed every 12 weeks from the first day of SRS/SRT, up to 12 months
Intracranial disease control rate (iDCR)
Proportion of participants with a best intracranial response of iCR, iPR or stable disease (iSD) according to RANO-BM.
Time frame: Assessed every 12 weeks from the first day of SRS/SRT, up to 12 months
Intracranial progression-free survival (iPFS)
Time in months from the first day of SRS/SRT to first documented intracranial progression according to RANO-BM or death from any cause, whichever occurs first. Participants without an event are censored at the date of the last adequate brain imaging assessment. Median estimated by the Kaplan-Meier method.
Time frame: From the first day of SRS/SRT until the date of first documented intracranial progression (RANO-BM) or death from any cause, whichever came first, assessed every 12 weeks up to 36 months
Intracranial Progression-Free Survival Rate at 6 Months
Percentage of participants alive and free of intracranial progression according to RANO-BM at 6 months after the first day of SRS/SRT, estimated by the Kaplan-Meier method.
Time frame: 6 months after the first day of SRS/SRT
Intracranial Progression-Free Survival Rate at 12 Months
Percentage of participants alive and free of intracranial progression according to RANO-BM at 12 months after the first day of SRS/SRT, estimated by the Kaplan-Meier method.
Time frame: 12 months after the first day of SRS/SRT
Progression-free survival (PFS)
Time in months from the first day of SRS/SRT to first documented progression at any site (intracranial according to RANO-BM or extracranial according to RECIST 1.1) or death from any cause, whichever occurs first. Participants without an event are censored at the date of the last adequate assessment. Median estimated by the Kaplan-Meier method.
Time frame: From the first day of SRS/SRT until the date of first documented progression at any site (RANO-BM or RECIST 1.1) or death from any cause, whichever came first, assessed every 12 weeks up to 36 months
Progression-Free Survival Rate at 12 Months
Percentage of participants alive and free of progression at any site (RANO-BM or RECIST 1.1) at 12 months after the first day of SRS/SRT, estimated by the Kaplan-Meier method.
Time frame: 12 months after the first day of SRS/SRT
Number of Participants With Osimertinib-Related Adverse Events
Number of participants with at least one osimertinib-related adverse event graded by CTCAE v5.0, including rash, mucositis, paronychia, diarrhoea, pneumonitis/interstitial lung disease, QTc prolongation, decreased left ventricular ejection fraction, keratitis, anaemia, neutropenia and thrombocytopenia.
Time frame: From the first day of SRS/SRT, assessed every 4 weeks, up to 36 months
Number of Participants With Acute SRS/SRT-Related Adverse Events
Number of participants with at least one acute radiation-related adverse event graded by CTCAE v5.0, including fatigue, headache, nausea/vomiting, cerebral oedema and seizure.
Time frame: From the first fraction of SRS/SRT up to 90 days after the last fraction
Number of Participants With Late SRS/SRT-Related Adverse Events
Number of participants with at least one late radiation-related adverse event graded by CTCAE v5.0, including radiation necrosis and intracranial haemorrhage.
Time frame: From day 91 after the last SRS/SRT fraction, assessed up to 36 months
Overall survival (OS)
Time in months from the first day of SRS/SRT to death from any cause. Participants alive at the time of analysis are censored at the last date known to be alive. Median estimated by the Kaplan-Meier method.
Time frame: From the first day of SRS/SRT until the date of death from any cause, assessed up to 36 months
Overall Survival Rate at 12 Months
Percentage of participants alive at 12 months after the first day of SRS/SRT, estimated by the Kaplan-Meier method.
Time frame: 12 months after the first day of SRS/SRT
Plan to share: Undecided
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