A Study of Stereotactic Radiosurgery (SRS) and Standard Treatment in People With Lung Cancer That Has Spread to the Brain

NCT06741085 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-378
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 8

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• intracranial progression-free survival (iPFS)

  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

  3 months

Secondary Outcomes (1)

• Time to CNS progression

  9 months

Study Arms (2)

osimertinib and stereotactic radiosurgery (SRS)

EXPERIMENTAL

Drug: osimertinib; Radiation: stereotactic radiosurgery (SRS)

osimertinib alone (standard systemic therapy)

ACTIVE COMPARATOR

Drug: osimertinib

Interventions

osimertinib DRUG

oral EGFR-TKI

osimertinib alone (standard systemic therapy); osimertinib and stereotactic radiosurgery (SRS)

stereotactic radiosurgery (SRS) RADIATION

0-20mm-18Gy x 1, 21Gy x 1 ,9Gy x 3 20mm or larger- 9Gy x 3, 6Gy x 5, 5Gy x 5

osimertinib and stereotactic radiosurgery (SRS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• \- Presence of detectable and non-progressing BM lesions on imaging consistent with viable residual disease
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (8)

BAPTIST ALLIANCE - MCI (Data Collection Only)

Miami, Florida, 33143, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Rockville Centre, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

osimertinib; Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Luke Pike, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luke Pike, MD

CONTACT

212-639-8157; pikel@mskcc.org

Helena Yu, MD

CONTACT

646-608-3912

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: December 18, 2024
• Study Start: December 13, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8)