Recruiting
Phase 2

Osimertinib vs. SRS

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT06741085

Conditions

Non Small Cell Lung Cancer Metastatic

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

osimertinib

stereotactic radiosurgery (SRS)

Study Details

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.

Conditions

Non Small Cell Lung Cancer Metastatic

Study ID

NCT06741085

Start date

Dec 13, 2024

Status verified date

Jun, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Exclusion Criteria: Randomization

  • Progressive Disease (PD) with multiple lesions and/or other features that would warrant a change in systemic therapy, as determined by the primary treating provider
  • Presence of BM not deemed safely treatable with SRS, as determined by a radiation oncologist
  • Intracranial Complete Response (CR)
  • More than 20 visible residual brain metastases at the time of enrollment (i.e. after initial treatment with TKI). However, no upper limit on the number of visible brain metastases is set at the time of initial diagnosis prior to treatment with TKI. For example, a patient who had 35 visible brain metastases at the time of diagnosis, but after three months of treatment with TKI had 10 visible brain metastases remaining will be eligible for enrollment and randomization

Study Design

Enrollment

56 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: osimertinib and stereotactic radiosurgery (SRS)

active comparator: osimertinib alone (standard systemic therapy)

Interventions

osimertinib

oral EGFR-TKI

stereotactic 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

Primary outcome measure

  • intracranial progression-free survival (iPFS) [ Time Frame: 3 months ]

Central Contacts and Locations

Central contacts

Luke Pike, MD

212-639-8157pikel@mskcc.org

Helena Yu, MD

646-608-3912

Locations

BAPTIST ALLIANCE - MCI (Data Collection Only)

Recruiting

Miami, Florida, United States, 33143

Contacts

Rupesh Kotecha, MD

786-596-2000

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Luke Pike, MD

212-639-8157

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Luke Pike, MD

212-639-8157

Memorial Sloan Kettering Bergen (All Protocol Activities)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Luke Pike, MD

212-639-8157

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Recruiting

Commack, New York, United States, 11725

Contacts

Luke Pike, MD

212-639-8157

Memorial Sloan Kettering Westchester (All Protocol Activities)

Recruiting

Harrison, New York, United States, 10604

Contacts

Luke Pike, MD

212-639-8157

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Recruiting

New York, New York, United States, 10065

Contacts

Luke Pike, MD

212-639-8157

Memorial Sloan Kettering Nassau (All Protocol Activities)

Recruiting

Rockville Centre, New York, United States, 11553

Contacts

Luke Pike, MD

212-639-8157

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Jun 17, 2026

Last verified

Jun, 2026

Keywords

  • somatic activating mutation in EGFR
  • consolidative stereotactic radiosurgery
  • tyrosine-kinase inhibitor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-06-17.