Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial
Start Date
3/4/2025
Completion Date
7/31/2028
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.
Detailed Description
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
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Computed Tomography
Involved-Field Radiation Therapy
Lumbar Puncture
Magnetic Resonance Imaging
Positron Emission Tomography
Proton Beam Craniospinal Irradiation
Quality-of-Life Assessment
Conditions
Locations
Mayo Clinic Hospital in Arizona
Phoenix, Arizona 85054
United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
United States
UC San Diego Health System - Encinitas
Encinitas, California 92024
United States
UC San Diego Moores Cancer Center
La Jolla, California 92093
United States
UC San Diego Medical Center - Hillcrest
San Diego, California 92103
United States
California Protons Cancer Therapy Center
San Diego, California 92121
United States
Sibley Memorial Hospital
Washington D.C., District of Columbia 20016
United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida 33180
United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida 33166
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
Miami Cancer Institute
Miami, Florida 33176
United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida 33176
United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
United States
Alton Memorial Hospital
Alton, Illinois 62002
United States
Northwestern University
Chicago, Illinois 60611
United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois 60115
United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134
United States
Memorial Hospital East
Shiloh, Illinois 62269
United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois 60555
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
United States
McLaren Cancer Institute-Flint
Flint, Michigan 48532
United States
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan 48910
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
Mercy Hospital Springfield
Springfield, Missouri 65804
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Mercy Hospital South
St Louis, Missouri 63128
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
NYU Langone Hospital - Brooklyn
Brooklyn, New York 11220
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Memorial Sloan Kettering Westchester
Harrison, New York 10604
United States
NYU Langone Hospital - Long Island
Mineola, New York 11501
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
New York Proton Center
New York, New York 10035
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York 10461
United States
Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
United States
Memorial Sloan Kettering Nassau
Uniondale, New York 11553
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
United States
Inova Alexandria Hospital
Alexandria, Virginia 22304
United States
Inova Schar Cancer Institute
Fairfax, Virginia 22031
United States
Inova Fair Oaks Hospital
Fairfax, Virginia 22033
United States
Inova Loudoun Hospital
Leesburg, Virginia 20176
United States