Back to search results

RADIATE-LM Trial: Proton vs. Standard Radiation for Leptomeningeal Metastasis

This study, called RADIATE-LM, is comparing two types of radiation therapy for breast or non-small cell lung cancer that has spread to the fluid around the brain and spinal cord (leptomeningeal metastasis). It's testing proton craniospinal irradiation (pCSI) against involved-field radiation therapy (IFRT), which is the usual treatment. The goal is to see if one treatment helps people live longer. The study is also looking at how well each treatment controls the cancer in the brain and spine, and what side effects people experience. To join, you must have breast cancer or non-small cell lung cancer that has recently spread to the leptomeninges, confirmed by a lab test of your spinal fluid. The study plans to enroll 115 participants, but its current status is unclear.

Study design
This is an interventional study comparing two radiation therapies. It plans to enroll 115 participants.
What's involved
You would undergo blood and spinal fluid collection, CT or PET/CT scans, involved-field radiation therapy, lumbar punctures, and MRI scans.
Compensation
Not stated in the trial record.
Follow-up
Your overall survival will be tracked from randomization until death, for up to 3 years.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06500481

Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial

Recruiting
PHASE3Ages 18+InterventionalTreatment
NRG Oncology
~115 participants
Updated 2026-08-17 on ClinicalTrials.gov
What's tested:Biospecimen CollectionComputed TomographyInvolved-Field Radiation TherapyLumbar PunctureMagnetic Resonance ImagingPositron Emission Tomography

At a glance

Recruiting sites
58 of 58 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall survival (OS)
Measured over From randomization until death due to any cause, assessed up to 3 years

Conditions

Anatomic Stage IV Breast Cancer AJCC v8
Metastatic Breast Carcinoma
Metastatic Lung Non-Small Cell Carcinoma
Metastatic Malignant Neoplasm in the Leptomeninges
Stage IV Lung Cancer AJCC v8

Explore related trials

Breast CarcinomaLung Non-Small Cell CarcinomaMetastatic Malignant Neoplasm in the Leptomeninges

Where it's being run

58 sites across 17 states
New York10
Missouri9
Florida8
Illinois6
California4
Michigan4
Virginia4
New Jersey3

Study leadership

  • Jonathan T Yang · PRINCIPAL_INVESTIGATOR · NRG Oncology

Who to contact

Site Public Contact
855-776-0015
Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

Check eligibility for this trial ~2 min · HIPAA-protected · delete anytime
Eligibility criteria

Inclusion

PRIOR TO STEP 1 REGISTRATION
Patients with pathologically (histologically or cytologically) proven diagnosis of breast cancer or NSCLC
Patients must have newly diagnosed leptomeningeal metastasis established through at least one of the following:
Positive CSF cytology for malignancy
CSF cytology with suspicious cells is considered positive; CSF cytology with atypical cells is considered equivocal and not positive
Patients with an equivocal or negative CSF cytology result, or not suitable for CSF sampling, radiographic diagnosis of leptomeningeal metastasis with linear and/or nodular disease and documentation of typical clinical signs (European Association of Neuro-Oncology \[EANO\]-European Society for Medical Oncology \[ESMO\] Diagnostic Criteria Type IIA-IIC) is required
Patients with typical clinical signs of leptomeningeal metastasis may have one or more of the following symptoms and signs: headache, nausea, vomiting, mental status change, gait difficulty, cranial nerve palsy, diplopia, visual change, hearing loss, radicular weakness, radicular sensory change, urinary retention, saddle anesthesia, constipation, neck pain, and back pain
For patients with prior history of immunotherapy or current immunotherapy, CSF sampling rather than just MRI enhancement is strongly recommended to exclude immune-related aseptic meningitis
Patients must be candidates for radiation therapy for the treatment of leptomeningeal metastasis
Age ≥ 18
PRIOR TO STEP 2 REGISTRATION
Note: Step 2 registration must occur no later than 30 calendar days after step 1 registration
Financial clearance for proton therapy treatment
Patients must have systemic disease evaluation through standard of care imaging for example CT chest/abdomen/pelvis or body PET/CT
Karnofsky performance status ≥ 60
Not pregnant and not nursing
Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dl is acceptable)
Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (Note: the use of granulocyte-colony stimulating factor or other intervention to achieve ANC ≥ 1,000/mm\^3 is acceptable)
Platelets ≥ 100,000/mm\^3 (Note: the use of transfusion or other intervention to achieve platelets ≥ 100,000/mm\^3 is acceptable)
Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (patients with known Gilbert disease without other clinically significant liver abnormalities are not excluded)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × ULN
No prior radiation therapy to the spinal cord with equivalent dose in 2 gray (Gy) fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using alpha/beta ratio of 3
No prior treatment for leptomeningeal metastasis (note: prior CNS treatment for other non-leptomeningeal disease is allowed)
No history of unstable angina requiring hospitalization in the last 3 months
No history of myocardial infarction within the last 3 months
New York Heart Association Functional Classification II or better (New York Heart Association \[NYHA\] Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
No active infection currently requiring intravenous (IV) antibiotic management
No active chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy
No CTCAE v5.0 ≥ grade 2 encephalopathy

What this trial measures

  • Overall survival (OS)From randomization until death due to any cause, assessed up to 3 years

    Will be event-driven and will be conducted when a total of 88 OS events (from both treatment arms) have been observed. The final analysis (if the trial does not stop early at an interim) is expected to occur roughly 45 months after study activation (including the initial 6-months ramp-up). All analyses (interim or final) will be done on a modified intent-to-treat (ITT) basis such that all randomized patients who have follow-up information will be included in the arm to which they are randomized regardless of what treatment the patients receive. Treatment comparisons will be based on the log-rank test. At the final analysis, if the test has an associated 1-sided p-value of 0.024 or less in favor of proton craniospinal irradiation (pCSI) (equivalently, Z \> 1.98), then the trial will conclude that the pCSI arm results in improved survival over the involved field radiotherapy (IFRT) arm.