Non Small Cell Lung Cancer Metastatic
Conditions
Keywords
somatic activating mutation in EGFR, consolidative stereotactic radiosurgery, tyrosine-kinase inhibitor
Brief summary
The researchers are doing this study is to find out whether treating brain metastasis with SRS after 3 months of therapy with osimertinib is better than treating with osimertinib alone in people with NSCLC. The researchers will also look at how the study intervention impacts participants' quality of life. The researchers will measure quality of life by having participants complete questionnaires.
Detailed description
Patients in both arms of this study will receive standard of care (SOC) systemic therapy which includes a backbone of an FDA-approved CNS-active TKI targeting mutant EGFR, specifically osimertinib.
Interventions
DRUGosimertinib
oral EGFR-TKI
RADIATIONstereotactic radiosurgery (SRS)
0-20mm-18Gy x 1, 21Gy x 1 ,9Gy x 3 20mm or larger- 9Gy x 3, 6Gy x 5, 5Gy x 5
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
After 3 months of TKI therapy, eligible patients are randomized to either continuing drug therapy alone with salvage interventions at progression (SOC) vs continuing drug therapy with addition of consolidative SRS of radiographically visible brain lesions (intervention). Randomization will be stratified by receipt of TKI monotherapy vs. TKI combination therapy (e.g. with concurrent chemotherapy) as first line systemic therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant Inclusion Criteria: Screening * Age ≥ 18 years * Non-small cell lung cancer (NSCLC) with somatic activating mutation in EGFR diagnosis, confirmed at enrolling institution * At least one intact brain metastasis at baseline prior to TKI therapy initiation, visible on MRI brain with contrast (but without a minimum diameter requirement) * Either TKI-naïve or started TKI ≤ 3-months prior (with documented start date and available imaging prior to TKI start) Participant
Exclusion criteria
Screening * Unable to undergo contrast-enhanced MRI brain * Prior brain-directed radiotherapy * Evidence of leptomeningeal disease on MRI total spine and/or lumbar puncture cytology. The latter are not mandated by protocol but are rather at the discretion of the treating medical team as clinically indicated. * Neurologic symptoms or presence of a lesion in the brainstem, motor strip, or other eloquent brain area that is felt to warrant immediate intervention with SRS * Active hematologic malignancy or a second solid tumor histology with known CNS tropism * Patients who have undergone a therapeutic craniotomy for resection of one or more symptomatic brain metastasis are ineligible unless one or more additional intact BM remain unresected, and meets size criteria (e.g., a patient with removal of a 3cm symptomatic brain metastasis, but has an additional visible lesion remaining post-operatively, remains eligible for the study). * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. * Pregnant women or women who are breastfeeding or of childbearing potential. If the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 3 months after last treatment. Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent) Participant Inclusion Criteria: Randomization \- Presence of detectable and non-progressing BM lesions on imaging consistent with viable residual disease Participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| intracranial progression-free survival (iPFS) | 3 months | Intracranial progression will be assessed at 3-month intervals and is defined as a ≥20% increase in sum longest distance relative to nadir for target lesions (up to a max of 5 lesions; must include at least one lesion increased in size by an absolute value of 5mm), unequivocal progression of non-target lesions, and/or the presence of new lesions, as defined by the RANO-BM working group criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to CNS progression | 9 months | defined as ≥20% increase in sum longest distance relative to nadir for target lesions (up to a max of 5 lesions; must include at least one lesion increased in size by an absolute value of 5mm), unequivocal progression of non-target lesions, and/or the presence of new lesions, as per RANO-BM (22). Death from any cause will be considered a competing risk. |
Countries
United States
Contacts
CONTACTLuke Pike, MD
CONTACTHelena Yu, MD
PRINCIPAL_INVESTIGATORLuke Pike, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed