Recruiting
Phase 3

Proton Craniospinal Radiation Therapy vs. Usual Radiation Therapy

Sponsor:

NRG Oncology

Code:

NCT06500481

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Involved-Field Radiation Therapy

Lumbar Puncture

Magnetic Resonance Imaging

Study Details

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

Study ID

NCT06500481

Start date

Mar 4, 2025

Status verified date

Aug, 2026

Completion date

Jul 31, 2033

Anticipated

Primary completion date

Jul 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

115 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm 1 (IFRT)

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.

experimental: Arm 2 (pCSI)

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.

Interventions

Biospecimen Collection

Undergo blood and CSF sample collection

Computed Tomography

Undergo CT or PET/CT

Involved-Field Radiation Therapy

Undergo IFRT

Lumbar Puncture

Undergo LP

Magnetic Resonance Imaging

Undergo MRI

Positron Emission Tomography

Undergo PET/CT

Proton Beam Craniospinal Irradiation

Undergo pCSI

Quality-of-Life Assessment

Ancillary studies

Primary outcome measure

  • Overall survival (OS) [ Time Frame: From randomization until death due to any cause, assessed up to 3 years ]

Central Contacts and Locations

Locations

Mayo Clinic Hospital in Arizona

Recruiting

Phoenix, Arizona, United States, 85054

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Eric Lehrer

University of Arkansas for Medical Sciences

Recruiting

Little Rock, Arkansas, United States, 72205

Contacts

Site Public Contact

501-686-8274

Principal Investigator:

Fen Xia

UC San Diego Health System - Encinitas

Recruiting

Encinitas, California, United States, 92024

Contacts

Site Public Contact

760-536-7700

Principal Investigator:

Jona A. Hattangadi-Gluth

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

Contacts

Site Public Contact

858-822-5354cancercto@ucsd.edu

Principal Investigator:

Jona A. Hattangadi-Gluth

UC San Diego Medical Center - Hillcrest

Recruiting

San Diego, California, United States, 92103

Contacts

Site Public Contact

rhabbaba@health.ucsd.edu

Principal Investigator:

Jona A. Hattangadi-Gluth

California Protons Cancer Therapy Center

Recruiting

San Diego, California, United States, 92121

Contacts

Site Public Contact

858-299-5982

Principal Investigator:

Jona A. Hattangadi-Gluth

Sibley Memorial Hospital

Recruiting

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

Contacts

Site Public Contact

202-243-2373jquiver1@jhmi.edu

Principal Investigator:

Carmen Kut

UM Sylvester Comprehensive Cancer Center at Aventura

Recruiting

Aventura, Florida, United States, 33180

Contacts

Site Public Contact

954-461-2180

Principal Investigator:

Morgan Freret

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Morgan Freret

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Morgan Freret

UM Sylvester Comprehensive Cancer Center at Doral

Recruiting

Doral, Florida, United States, 33166

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Morgan Freret

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Morgan Freret

Miami Cancer Institute

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

786-596-2000

Principal Investigator:

Matthew D. Hall

UM Sylvester Comprehensive Cancer Center at Kendall

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Morgan Freret

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Morgan Freret

Alton Memorial Hospital

Recruiting

Alton, Illinois, United States, 62002

Contacts

Site Public Contact

618-463-7323

Principal Investigator:

Nikhil Rammohan

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Site Public Contact

312-695-1301cancer@northwestern.edu

Principal Investigator:

Vinai Gondi

Northwestern Medicine Cancer Center Kishwaukee

Recruiting

DeKalb, Illinois, United States, 60115

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Vinai Gondi

Northwestern Medicine Cancer Center Delnor

Recruiting

Geneva, Illinois, United States, 60134

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Vinai Gondi

Memorial Hospital East

Recruiting

Shiloh, Illinois, United States, 62269

Contacts

Site Public Contact

314-747-9912dschwab@wustl.edu

Principal Investigator:

Nikhil Rammohan

Northwestern Medicine Cancer Center Warrenville

Recruiting

Warrenville, Illinois, United States, 60555

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Vinai Gondi

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

University of Kansas Cancer Center-Overland Park

Recruiting

Overland Park, Kansas, United States, 66210

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Site Public Contact

410-955-8804jhcccro@jhmi.edu

Principal Investigator:

Carmen Kut

Wayne State University/Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Site Public Contact

800-527-6266ctoadmin@karmanos.org

Principal Investigator:

Brian K. Yeh

Weisberg Cancer Treatment Center

Recruiting

Farmington Hills, Michigan, United States, 48334

Contacts

Site Public Contact

313-576-9790ctoadmin@karmanos.org

Principal Investigator:

Brian K. Yeh

McLaren Cancer Institute-Flint

Recruiting

Flint, Michigan, United States, 48532

Contacts

Site Public Contact

313-576-9790ctoadmin@karmanos.org

Principal Investigator:

Brian K. Yeh

Karmanos Cancer Institute at McLaren Greater Lansing

Recruiting

Lansing, Michigan, United States, 48910

Contacts

Site Public Contact

313-576-9790ctoadmin@karmanos.org

Principal Investigator:

Brian K. Yeh

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Eric Lehrer

Siteman Cancer Center at Saint Peters Hospital

Recruiting

City of Saint Peters, Missouri, United States, 63376

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Nikhil Rammohan

Siteman Cancer Center at West County Hospital

Recruiting

Creve Coeur, Missouri, United States, 63141

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Nikhil Rammohan

University of Kansas Cancer Center - North

Recruiting

Kansas City, Missouri, United States, 64154

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

University of Kansas Cancer Center - Lee's Summit

Recruiting

Lee's Summit, Missouri, United States, 64064

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

Mercy Hospital Springfield

Recruiting

Springfield, Missouri, United States, 65804

Contacts

Site Public Contact

417-269-4520

Principal Investigator:

Jay W. Carlson

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Nikhil Rammohan

Mercy Hospital South

Recruiting

St Louis, Missouri, United States, 63128

Contacts

Site Public Contact

314-525-6042Danielle.Werle@mercy.net

Principal Investigator:

Jay W. Carlson

Siteman Cancer Center-South County

Recruiting

St Louis, Missouri, United States, 63129

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Nikhil Rammohan

Siteman Cancer Center at Christian Hospital

Recruiting

St Louis, Missouri, United States, 63136

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Nikhil Rammohan

Memorial Sloan Kettering Basking Ridge

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

Memorial Sloan Kettering Monmouth

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

Memorial Sloan Kettering Bergen

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

NYU Langone Hospital - Brooklyn

Recruiting

Brooklyn, New York, United States, 11220

Contacts

Site Public Contact

646-754-4624david.wallach@nyulangone.org

Principal Investigator:

Jonathan T. Yang

Memorial Sloan Kettering Commack

Recruiting

Commack, New York, United States, 11725

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

Memorial Sloan Kettering Westchester

Recruiting

Harrison, New York, United States, 10604

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

NYU Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

Contacts

Site Public Contact

212-263-4432cancertrials@nyulangone.org

Principal Investigator:

Jonathan T. Yang

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Contacts

Site Public Contact

CancerTrials@nyulangone.org

Principal Investigator:

Jonathan T. Yang

New York Proton Center

Recruiting

New York, New York, United States, 10035

Contacts

Site Public Contact

646-968-9031ichoi@nyproton.com

Principal Investigator:

Arpit M. Chhabra

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

Montefiore Medical Center-Einstein Campus

Recruiting

The Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Jana L. Fox

Montefiore Medical Center - Moses Campus

Recruiting

The Bronx, New York, United States, 10467

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Jana L. Fox

Memorial Sloan Kettering Nassau

Recruiting

Uniondale, New York, United States, 11553

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Yao Yu

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Joshua D. Palmer

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Jerry J. Jaboin

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100cancerinfo@hci.utah.edu

Principal Investigator:

Rachna Malani

Inova Alexandria Hospital

Recruiting

Alexandria, Virginia, United States, 22304

Contacts

Site Public Contact

703-776-2580Stephanie.VanBebber@inova.org

Principal Investigator:

Avani D. Rao

Inova Schar Cancer Institute

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Site Public Contact

703-720-5210Stephanie.VanBebber@inova.org

Principal Investigator:

Avani D. Rao

Inova Fair Oaks Hospital

Recruiting

Fairfax, Virginia, United States, 22033

Contacts

Site Public Contact

703-720-5210Stephanie.VanBebber@inova.org

Principal Investigator:

Avani D. Rao

Inova Loudoun Hospital

Recruiting

Leesburg, Virginia, United States, 20176

Contacts

Site Public Contact

703-858-6000Keary.janet@inova.org

Principal Investigator:

Avani D. Rao

More Information

Sponsor

NRG Oncology

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by NRG Oncology on 2026-08-17.