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Comparing proton radiation therapy to standard radiation for leptomeningeal metastasis

A Phase III Randomized Clinical Trial of Proton Craniospinal Irradiation Versus Involved-Field Radiotherapy for Patients With Breast Cancer or Non-Small Cell Lung Cancer Leptomeningeal Metastasis (Radiate-LM)

PHASE3 · NRG Oncology · NCT06500481

This study is testing whether proton radiation therapy is better than standard radiation for people with leptomeningeal metastasis from breast or lung cancer to see if it helps them live longer and stay healthier.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment115 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology (other)
Drugs / interventionsimmunotherapy, radiation
Locations58 sites (Phoenix, Arizona and 57 other locations)
Trial IDNCT06500481 on ClinicalTrials.gov

What this trial studies

This phase III trial evaluates the effectiveness of proton craniospinal irradiation (pCSI) compared to involved-field radiation therapy (IFRT) in patients with leptomeningeal metastasis resulting from breast or non-small cell lung cancer. The study aims to determine overall survival rates and central nervous system progression-free survival between the two treatment methods. Patients will undergo various assessments, including imaging and symptom reporting, to evaluate treatment outcomes and side effects. The trial seeks to provide insights into the potential advantages of using protons for more targeted radiation treatment.

Who should consider this trial

Good fit: Ideal candidates include patients with newly diagnosed leptomeningeal metastasis from breast cancer or non-small cell lung cancer.

Not a fit: Patients with leptomeningeal metastasis from other cancer types or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved survival rates and quality of life for patients with leptomeningeal metastasis.

How similar studies have performed: While there have been studies on radiation therapies for leptomeningeal metastasis, the use of proton therapy in this context is relatively novel and not extensively tested.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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

Where this trial is running

Phoenix, Arizona and 57 other locations

+8 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

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

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.