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

NCT06500481 | Recruiting Phase 3

• 3 other identifiers: NRG-BN014NCI-2024-04895U10CA180868
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 57

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  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.

  From randomization until death due to any cause, assessed up to 3 years

Secondary Outcomes (5)

• Central nervous system (CNS) progression-free survival (PFS)

  Randomization until CNS progression or death, whichever occurs first, assessed up to 3 years

• Time to CNS progression

  Randomization until CNS progression, assessed up to 3 years

• Time to radiation-induced CNS necrosis (TTRN)

  Randomization until radiation necrosis in brain and/or spinal cord, assessed up to 3 years

• Incidence of treatment-related adverse events (AEs)

  Baseline to 30 days from end of radiation therapy

• Patient reported outcomes (PRO)

  Baseline to 24 months post-radiation therapy

Other Outcomes (3)

• Estimates of the primary outcome treatment effect by sex

  Up to 3 years

• Estimates of the primary outcome treatment effect by race

  Up to 3 years

• Estimates of the primary outcome treatment effect by ethnicity

  Up to 3 years

Study Arms (2)

Arm 1 (IFRT)

ACTIVE COMPARATOR

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 CT or PET/CT during screening and MRI as well as LP throughout the study. Patients may optionally undergo research blood sample and CSF collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Involved-Field Radiation Therapy; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment

Arm 2 (pCSI)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Proton Beam Craniospinal Irradiation; Other: Quality-of-Life Assessment

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (IFRT); Arm 2 (pCSI)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm 1 (IFRT); Arm 2 (pCSI)

Lumbar Puncture PROCEDURE

Undergo LP

Also known as: LP, Spinal Tap

Arm 1 (IFRT); Arm 2 (pCSI)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (IFRT); Arm 2 (pCSI)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm 1 (IFRT); Arm 2 (pCSI)

Proton Beam Craniospinal Irradiation RADIATION

Undergo pCSI

Also known as: Craniospinal Proton Beam Radiation Therapy, p-CSI, Proton Craniospinal Irradiation, Proton Craniospinal Radiation Therapy

Arm 2 (pCSI)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm 1 (IFRT); Arm 2 (pCSI)

Involved-Field Radiation Therapy RADIATION

Undergo IFRT

Also known as: IFRT, Involved field radiotherapy

Arm 1 (IFRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• NRG Oncology: lead

Study Sites (57)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

UC San Diego Health System - Encinitas

Encinitas, California, 92024, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

RECRUITING

California Protons Cancer Therapy Center

San Diego, California, 92121, United States

RECRUITING

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, 33166, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176, United States

RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

RECRUITING

Alton Memorial Hospital

Alton, Illinois, 62002, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115, United States

RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134, United States

RECRUITING

Memorial Hospital East

Shiloh, Illinois, 62269, United States

RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

RECRUITING

McLaren Cancer Institute-Flint

Flint, Michigan, 48532, United States

RECRUITING

Karmanos Cancer Institute at McLaren Greater Lansing

Lansing, Michigan, 48910, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

RECRUITING

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

RECRUITING

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

RECRUITING

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Mercy Hospital South

St Louis, Missouri, 63128, United States

RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

NYU Langone Hospital - Brooklyn

Brooklyn, New York, 11220, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

RECRUITING

New York Proton Center

New York, New York, 10035, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Inova Alexandria Hospital

Alexandria, Virginia, 22304, United States

RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

RECRUITING

Inova Fair Oaks Hospital

Fairfax, Virginia, 22033, United States

RECRUITING

Inova Loudoun Hospital

Leesburg, Virginia, 20176, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis; Lung Neoplasms

Interventions

Specimen Handling; Spinal Puncture; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jonathan T Yang

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 15, 2024
• Study Start: March 4, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (57)