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

NCT06500481 · NRG Oncology
In plain English

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Official title
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)
About this study
PRIMARY OBJECTIVE: I. To compare overall survival (OS) between proton craniospinal irradiation (pCSI) and involved-field radiotherapy (IFRT) in patients with breast cancer or non-small cell lung cancer (NSCLC) leptomeningeal metastasis. SECONDARY OBJECTIVES: I. To compare central nervous system progression-free survival (CNS PFS) between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis. II. To compare time to CNS progression between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis. III. To compare CNS PFS between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis, as evaluated by central review of imaging. IV. To compare the rate of radiation-induced central nervous system necrosis between pCSI versus (vs.) IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis. V. To characterize treatment-related adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. VI. To compare patient-reported outcomes (symptoms severity subscale per MD Anderson Symptom Inventory for Brain Tumors \[MDASI-BT\] and MD Anderson Symptom Inventory for Spine Tumors \[MDASI-SP\]) in patients with breast cancer or non-small cell lung cancer leptomeningeal metastasis. EXPLORATORY OBJECTIVE: I. To compare patient-reported outcomes (symptoms interference, brain tumor-specific, spine tumor-specific subscales per MDASI-BT and MDASI-SP) in patients with breast cancer or non-small cell lung cancer leptomeningeal metastasis. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients undergo involved-field radiation therapy delivered to specific areas of LM that are causing and/or may cause symptoms 5 days a week for a total of 10 days of treatment in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT during screening and magnetic resonance imaging (MRI) as well as possible lumbar puncture (LP) throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study. ARM 2: Patients undergo pCSI radiation therapy delivered to the entire space containing the CSF, brain, and spinal cord 5 days a week for a total of 10 days of treatment in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT during screening and MRI as well as possible LP throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study. After completion of study treatment, patients are followed every 3 months for 12 months, and then every 6 months for up to 3 years from end of RT.
Eligibility 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
Study design
Enrollment target: 115 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-03-04
Estimated completion: 2028-07-31
Last updated: 2026-05-07
Interventions
Procedure: Biospecimen CollectionProcedure: Computed TomographyRadiation: Involved-Field Radiation TherapyProcedure: Lumbar PunctureProcedure: Magnetic Resonance ImagingProcedure: Positron Emission TomographyRadiation: Proton Beam Craniospinal IrradiationOther: Quality-of-Life Assessment
Primary outcomes
  • Overall survival (OS) (From randomization until death due to any cause, assessed up to 3 years)
Sponsor
NRG Oncology · other
Contacts & investigators
InvestigatorJonathan T Yang · principal_investigator, NRG Oncology
All locations (58)
Mayo Clinic Hospital in ArizonaRecruiting
Phoenix, Arizona, United States
University of Arkansas for Medical SciencesRecruiting
Little Rock, Arkansas, United States
UC San Diego Health System - EncinitasRecruiting
Encinitas, California, United States
UC San Diego Moores Cancer CenterRecruiting
La Jolla, California, United States
UC San Diego Medical Center - HillcrestRecruiting
San Diego, California, United States
California Protons Cancer Therapy CenterRecruiting
San Diego, California, United States
Sibley Memorial HospitalRecruiting
Washington D.C., District of Columbia, United States
UM Sylvester Comprehensive Cancer Center at AventuraRecruiting
Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral GablesRecruiting
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield BeachRecruiting
Deerfield Beach, Florida, United States
UM Sylvester Comprehensive Cancer Center at DoralRecruiting
Doral, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
Miami, Florida, United States
Miami Cancer InstituteRecruiting
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at KendallRecruiting
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at PlantationRecruiting
Plantation, Florida, United States
Alton Memorial HospitalRecruiting
Alton, Illinois, United States
Northwestern UniversityRecruiting
Chicago, Illinois, United States
Northwestern Medicine Cancer Center KishwaukeeRecruiting
DeKalb, Illinois, United States
Northwestern Medicine Cancer Center DelnorRecruiting
Geneva, Illinois, United States
Memorial Hospital EastRecruiting
Shiloh, Illinois, United States
Northwestern Medicine Cancer Center WarrenvilleRecruiting
Warrenville, Illinois, United States
University of Kansas Cancer CenterRecruiting
Kansas City, Kansas, United States
University of Kansas Cancer Center-Overland ParkRecruiting
Overland Park, Kansas, United States
Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
Baltimore, Maryland, United States
Wayne State University/Karmanos Cancer InstituteRecruiting
Detroit, Michigan, United States
Weisberg Cancer Treatment CenterRecruiting
Farmington Hills, Michigan, United States
McLaren Cancer Institute-FlintRecruiting
Flint, Michigan, United States
Karmanos Cancer Institute at McLaren Greater LansingRecruiting
Lansing, Michigan, United States
Mayo Clinic in RochesterRecruiting
Rochester, Minnesota, United States
Siteman Cancer Center at Saint Peters HospitalRecruiting
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County HospitalRecruiting
Creve Coeur, Missouri, United States
University of Kansas Cancer Center - NorthRecruiting
Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's SummitRecruiting
Lee's Summit, Missouri, United States
Mercy Hospital SpringfieldRecruiting
Springfield, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Mercy Hospital SouthRecruiting
St Louis, Missouri, United States
Siteman Cancer Center-South CountyRecruiting
St Louis, Missouri, United States
Siteman Cancer Center at Christian HospitalRecruiting
St Louis, Missouri, United States
Memorial Sloan Kettering Basking RidgeRecruiting
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering MonmouthRecruiting
Middletown, New Jersey, United States
Memorial Sloan Kettering BergenRecruiting
Montvale, New Jersey, United States
NYU Langone Hospital - BrooklynRecruiting
Brooklyn, New York, United States
Memorial Sloan Kettering CommackRecruiting
Commack, New York, United States
Memorial Sloan Kettering WestchesterRecruiting
East White Plains, New York, United States
NYU Langone Hospital - Long IslandRecruiting
Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
New York, New York, United States
New York Proton CenterRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Montefiore Medical Center-Einstein CampusRecruiting
The Bronx, New York, United States
Montefiore Medical Center - Moses CampusRecruiting
The Bronx, New York, United States
Memorial Sloan Kettering NassauRecruiting
Uniondale, New York, United States
Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, United States
University of Oklahoma Health Sciences CenterRecruiting
Oklahoma City, Oklahoma, United States
Huntsman Cancer Institute/University of UtahRecruiting
Salt Lake City, Utah, United States
Inova Alexandria HospitalRecruiting
Alexandria, Virginia, United States
Inova Schar Cancer InstituteRecruiting
Fairfax, Virginia, United States
Inova Fair Oaks HospitalRecruiting
Fairfax, Virginia, United States
Inova Loudoun HospitalRecruiting
Leesburg, Virginia, United States
Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial · TrialPath