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NCT06500481PHASE3Recruiting

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

NRG Oncology

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

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

Interventions

PROCEDURE

Biospecimen Collection

PROCEDURE

Computed Tomography

RADIATION

Involved-Field Radiation Therapy

PROCEDURE

Lumbar Puncture

PROCEDURE

Magnetic Resonance Imaging

PROCEDURE

Positron Emission Tomography

RADIATION

Proton Beam Craniospinal Irradiation

OTHER

Quality-of-Life Assessment

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Conditions

Anatomic Stage IV Breast Cancer AJCC v8Metastatic Breast CarcinomaMetastatic Lung Non-Small Cell CarcinomaMetastatic Malignant Neoplasm in the LeptomeningesStage IV Lung Cancer AJCC v8

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