This study involves patients with EGFR-mutated NSCLC and asymptomatic brain metastases. This is an open-label, randomized study, comparing the continuation of Osimertinib treatment alone to Osimertinib treatment combined with early intervention stereotactic radiosurgery (SRS). The current first line of care for EGFR-mutated NSCLC is administration of Osimertinib, a small molecule that penetrates the blood brain barrier (BBB) well and controls majority, but not all, of the brain metastases. We hypothesize that relatively early intervention with SRS to brain metastases that are still visualized by MRI 2 months-post initiation of Osimertinib treatment, LUNG- will improve long term brain control, cognitive abilities and potentially overall survival. Patients with EGFR-mutated NSCLC and asymptomatic brain metastases will be treated with Osimertinib for 2 months. Brain MRI scans will be collected pre-Osimertinib and 2 months after treatment start. Patients with asymptomatic brain metastases present after 2 months of Osimertinib will be randomized into one of two study arms. Arm A patients will be treated with SRS while continuing Osimertinib, while arm B patients will continue with Osimertinib alone. Patients will be assessed based on brain and whole body progression by RECIST. Patients will also be assessed for CNS-PFS and body-PFS, cognitive function, Quality of life and overall survival status via routine follow-up tests.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
162
At two month (8 weeks) post Osimertinib start, patients will be randomized into one of the two study arms. Arm A patients will be treated with stereotactic surgery (SRS). In both arms Osimertinib treatment will continue.
Hadassah Ein Kerem Medical Center
Jerusalem, Israel
RECRUITINGBrain control: CNS-PFS
Lesions that did not disappear after two months of Osimertinib treatment will be better controlled with SRS
Time frame: Change in lesion size in the CNS will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
whole body PFS
Whole body progression will be delayed when Osimertinib is combined with early treatment of SRS
Time frame: Change in lesion size in the whole body will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Cognitive function
Patient cognitive function will improve after SRS treatment
Time frame: Change in patient cognitive function will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Quality of life (QOL)
Patient QOL will improve after SRS treatment
Time frame: Change in patient quality of life will be followed and assessed at screen, Randomization, 2 month after Randomization, then every 3 month
Time to whole brain radiation
Time until whole brain radiation will be given will prolong for patients who receive early SRS treatment
Time frame: Status will be checked at every visit and follow up
Overall survival (OS)
Patient OS will improve after SRS treatment
Time frame: Status will be checked at every visit and follow up
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