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

ICON-RT: Intracranial Consolidation and Deferral of Radiation Therapy in Patients Receiving Approved CNS-Active Systemic Therapeutics

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.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer Metastatic
• Intervention / Treatment: Drug: osimertinib; Radiation: stereotactic radiosurgery (SRS)

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.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Helena Yu, MD; Phone Number: 646-608-3912
• Study Contact Backup: Name: Luke Pike, MD; Phone Number: 212-639-8157; Email: pikel@mskcc.org

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • Recruiting
      • BAPTIST ALLIANCE - MCI (Data Collection Only)
      • Contact: Rupesh Kotecha, MD; Phone Number: 786-596-2000
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All Protocol Activities)
      • Contact: Luke Pike, MD; Phone Number: 212-639-8157

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: osimertinib and stereotactic radiosurgery (SRS)	Drug: osimertinib; oral EGFR-TKI; Radiation: 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
Active Comparator: osimertinib alone (standard systemic therapy)	Drug: osimertinib; oral EGFR-TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to CNS progression	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.	9 months

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Luke Pike, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: tyrosine-kinase inhibitor; somatic activating mutation in EGFR; consolidative stereotactic radiosurgery
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery; osimertinib
• Other Study ID Numbers: 24-378

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No