NCT06500481RecruitingPhase 3
Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial
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)
Source: ClinicalTrials.gov · Last updated 17 Aug 2026
Brief summary (registry, in English)
This phase III trial compares proton craniospinal irradiation (pCSI) to involved-field radiation therapy (IFRT) for the treatment of breast or non-small cell lung cancer that has spread from where it first started to the cerebrospinal fluid filled space that surrounds the brain and spinal cord (leptomeningeal metastasis). Patients with leptomeningeal metastasis (LM) may develop multiple areas of nervous system (neurologic) impairment that can be life-threatening. Radiation therapy (RT) effectively relieves local symptoms due to LM. RT uses high energy radiography (x-rays), particles, or radioactive seeds to kill cancer cells and shrink tumors. IFRT is commonly used to treat symptoms of LM. IFRT is radiation treatment that uses x-rays to treat specific areas of LM and to relieve and/or prevent symptoms. pCSI uses protons that can be directed with more accuracy than x-rays which allows treatment of the entire central nervous system space containing the cerebrospinal fluid (CSF), brain, and spinal cord. The pCSI treatment could delay the worsening of LM. Giving pCSI may be better than IFRT in treating LM in patients with breast or non-small cell lung cancer.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 3
- Study type
- Interventional
- Enrollment
- 115 (estimated)
- First submitted
- 8 Jul 2024
- Start date
- 4 Mar 2025
- Primary completion date
- 31 Jul 2028
- Lead sponsor
- NRG Oncology
- Diseases
- Lung cancer, Metastatic breast cancer
- NCT number
- NCT06500481
What you commit to
- Study type: Interventional · Phase 3
- Planned participants: 115
- From 4 Mar 2025 to the primary completion date, 31 Jul 2028
- 58 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Who the study is looking for
- 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
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (58)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Inova Alexandria Hospital Coordinator of this site? Confirm its status | Alexandria | United States | Recruiting |
| Alton Memorial Hospital Coordinator of this site? Confirm its status | Alton | United States | Recruiting |
| UM Sylvester Comprehensive Cancer Center at Aventura Coordinator of this site? Confirm its status | Aventura | United States | Recruiting |
| Johns Hopkins University/Sidney Kimmel Cancer Center Coordinator of this site? Confirm its status | Baltimore | United States | Recruiting |
| Memorial Sloan Kettering Basking Ridge Coordinator of this site? Confirm its status | Basking Ridge | United States | Recruiting |
| NYU Langone Hospital - Brooklyn Coordinator of this site? Confirm its status | Brooklyn | United States | Recruiting |
| Northwestern University Coordinator of this site? Confirm its status | Chicago | United States | Recruiting |
| Siteman Cancer Center at Saint Peters Hospital Coordinator of this site? Confirm its status | City of Saint Peters | United States | Recruiting |
| Ohio State University Comprehensive Cancer Center Coordinator of this site? Confirm its status | Columbus | United States | Recruiting |
| Memorial Sloan Kettering Commack Coordinator of this site? Confirm its status | Commack | United States | Recruiting |
| UM Sylvester Comprehensive Cancer Center at Coral Gables Coordinator of this site? Confirm its status | Coral Gables | United States | Recruiting |
| Siteman Cancer Center at West County Hospital Coordinator of this site? Confirm its status | Creve Coeur | United States | Recruiting |
| UM Sylvester Comprehensive Cancer Center at Deerfield Beach Coordinator of this site? Confirm its status | Deerfield Beach | United States | Recruiting |
| Northwestern Medicine Cancer Center Kishwaukee Coordinator of this site? Confirm its status | DeKalb | United States | Recruiting |
| Wayne State University/Karmanos Cancer Institute Coordinator of this site? Confirm its status | Detroit | United States | Recruiting |
| UM Sylvester Comprehensive Cancer Center at Doral Coordinator of this site? Confirm its status | Doral | United States | Recruiting |
| UC San Diego Health System - Encinitas Coordinator of this site? Confirm its status | Encinitas | United States | Recruiting |
| Inova Fair Oaks Hospital Coordinator of this site? Confirm its status | Fairfax | United States | Recruiting |
| Inova Schar Cancer Institute Coordinator of this site? Confirm its status | Fairfax | United States | Recruiting |
| Weisberg Cancer Treatment Center Coordinator of this site? Confirm its status | Farmington Hills | United States | Recruiting |
| McLaren Cancer Institute-Flint Coordinator of this site? Confirm its status | Flint | United States | Recruiting |
| Northwestern Medicine Cancer Center Delnor Coordinator of this site? Confirm its status | Geneva | United States | Recruiting |
| Memorial Sloan Kettering Westchester Coordinator of this site? Confirm its status | Harrison | United States | Recruiting |
| University of Kansas Cancer Center - North Coordinator of this site? Confirm its status | Kansas City | United States | Recruiting |
| University of Kansas Cancer Center Coordinator of this site? Confirm its status | Kansas City | United States | Recruiting |
| UC San Diego Moores Cancer Center Coordinator of this site? Confirm its status | La Jolla | United States | Recruiting |
| Karmanos Cancer Institute at McLaren Greater Lansing Coordinator of this site? Confirm its status | Lansing | United States | Recruiting |
| Inova Loudoun Hospital Coordinator of this site? Confirm its status | Leesburg | United States | Recruiting |
| University of Kansas Cancer Center - Lee's Summit Coordinator of this site? Confirm its status | Lee's Summit | United States | Recruiting |
| University of Arkansas for Medical Sciences Coordinator of this site? Confirm its status | Little Rock | United States | Recruiting |
| University of Miami Miller School of Medicine-Sylvester Cancer Center Coordinator of this site? Confirm its status | Miami | United States | Recruiting |
| UM Sylvester Comprehensive Cancer Center at Kendall Coordinator of this site? Confirm its status | Miami | United States | Recruiting |
| Miami Cancer Institute Coordinator of this site? Confirm its status | Miami | United States | Recruiting |
| Memorial Sloan Kettering Monmouth Coordinator of this site? Confirm its status | Middletown | United States | Recruiting |
| NYU Langone Hospital - Long Island Coordinator of this site? Confirm its status | Mineola | United States | Recruiting |
| Memorial Sloan Kettering Bergen Coordinator of this site? Confirm its status | Montvale | United States | Recruiting |
| Laura and Isaac Perlmutter Cancer Center at NYU Langone Coordinator of this site? Confirm its status | New York | United States | Recruiting |
| New York Proton Center Coordinator of this site? Confirm its status | New York | United States | Recruiting |
| Memorial Sloan-Kettering Cancer Center Coordinator of this site? Confirm its status | New York | United States | Recruiting |
| University of Oklahoma Health Sciences Center Coordinator of this site? Confirm its status | Oklahoma City | United States | Recruiting |
| University of Kansas Cancer Center-Overland Park Coordinator of this site? Confirm its status | Overland Park | United States | Recruiting |
| Mayo Clinic Hospital in Arizona Coordinator of this site? Confirm its status | Phoenix | United States | Recruiting |
| UM Sylvester Comprehensive Cancer Center at Plantation Coordinator of this site? Confirm its status | Plantation | United States | Recruiting |
| Mayo Clinic in Rochester Coordinator of this site? Confirm its status | Rochester | United States | Recruiting |
| Huntsman Cancer Institute/University of Utah Coordinator of this site? Confirm its status | Salt Lake City | United States | Recruiting |
| California Protons Cancer Therapy Center Coordinator of this site? Confirm its status | San Diego | United States | Recruiting |
| UC San Diego Medical Center - Hillcrest Coordinator of this site? Confirm its status | San Diego | United States | Recruiting |
| Memorial Hospital East Coordinator of this site? Confirm its status | Shiloh | United States | Recruiting |
| Mercy Hospital Springfield Coordinator of this site? Confirm its status | Springfield | United States | Recruiting |
| Siteman Cancer Center at Christian Hospital Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Washington University School of Medicine Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Siteman Cancer Center-South County Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Mercy Hospital South Coordinator of this site? Confirm its status | St Louis | United States | Recruiting |
| Montefiore Medical Center - Moses Campus Coordinator of this site? Confirm its status | The Bronx | United States | Recruiting |
| Montefiore Medical Center-Einstein Campus Coordinator of this site? Confirm its status | The Bronx | United States | Recruiting |
| Memorial Sloan Kettering Nassau Coordinator of this site? Confirm its status | Uniondale | United States | Recruiting |
| Northwestern Medicine Cancer Center Warrenville Coordinator of this site? Confirm its status | Warrenville | United States | Recruiting |
| Sibley Memorial Hospital Coordinator of this site? Confirm its status | Washington D.C. | United States | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.