AzTrials
AzTrials

Anatomic Stage IV Breast Cancer AJCC v8Phase 3NCT06500481

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

A Phase 3 study testing Biospecimen Collection, Computed Tomography and Involved-Field Radiation Therapy in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by NRG Oncology at 58 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Involved-Field Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
58 sitesUnited States
Study dates
4 Mar 2025to 31 Jul 2033
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

None listed.

Trial locations and contacts

58 sites in 1 country. Contact the study team or a site near you to ask about taking part.

58 sites in 1 country

United States58 sites, 58 recruiting

  • Inova Alexandria Hospital

    Alexandria, Virginia, 22304

    Site Public Contact, 703-776-2580, Stephanie.VanBebber@inova.org

    Avani D. Rao

    Recruiting

  • Alton Memorial Hospital

    Alton, Illinois, 62002

    Site Public Contact, 618-463-7323

    Nikhil Rammohan

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

    Site Public Contact, 954-461-2180

    Morgan Freret

    Recruiting

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

    Site Public Contact, 410-955-8804, jhcccro@jhmi.edu

    Carmen Kut

    Recruiting

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • NYU Langone Hospital - Brooklyn

    Brooklyn, New York, 11220

    Site Public Contact, 646-754-4624, david.wallach@nyulangone.org

    Jonathan T. Yang

    Recruiting

  • Northwestern University

    Chicago, Illinois, 60611

    Site Public Contact, 312-695-1301, cancer@northwestern.edu

    Vinai Gondi

    Recruiting

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Nikhil Rammohan

    Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Site Public Contact, 800-293-5066, Jamesline@osumc.edu

    Joshua D. Palmer

    Recruiting

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

    Site Public Contact, 305-243-2647

    Morgan Freret

    Recruiting

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Nikhil Rammohan

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

    Site Public Contact, 305-243-2647

    Morgan Freret

    Recruiting

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

    Site Public Contact, 630-352-5360, Donald.Smith3@nm.org

    Vinai Gondi

    Recruiting

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Site Public Contact, 800-527-6266, ctoadmin@karmanos.org

    Brian K. Yeh

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Doral

    Doral, Florida, 33166

    Site Public Contact, kginnity@med.miami.edu

    Morgan Freret

    Recruiting

  • UC San Diego Health System - Encinitas

    Encinitas, California, 92024

    Site Public Contact, 760-536-7700

    Jona A. Hattangadi-Gluth

    Recruiting

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

    Site Public Contact, 703-720-5210, Stephanie.VanBebber@inova.org

    Avani D. Rao

    Recruiting

  • Inova Fair Oaks Hospital

    Fairfax, Virginia, 22033

    Site Public Contact, 703-720-5210, Stephanie.VanBebber@inova.org

    Avani D. Rao

    Recruiting

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Brian K. Yeh

    Recruiting

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Brian K. Yeh

    Recruiting

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

    Site Public Contact, 630-352-5360, Donald.Smith3@nm.org

    Vinai Gondi

    Recruiting

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Danielle Cunningham

    Recruiting

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Danielle Cunningham

    Recruiting

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

    Site Public Contact, 858-822-5354, cancercto@ucsd.edu

    Jona A. Hattangadi-Gluth

    Recruiting

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

    Site Public Contact, 313-576-9790, ctoadmin@karmanos.org

    Brian K. Yeh

    Recruiting

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Danielle Cunningham

    Recruiting

  • Inova Loudoun Hospital

    Leesburg, Virginia, 20176

    Site Public Contact, 703-858-6000, Keary.janet@inova.org

    Avani D. Rao

    Recruiting

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

    Site Public Contact, 501-686-8274

    Fen Xia

    Recruiting

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

    Site Public Contact, 305-243-2647

    Morgan Freret

    Recruiting

  • Miami Cancer Institute

    Miami, Florida, 33176

    Site Public Contact, 786-596-2000

    Matthew D. Hall

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

    Site Public Contact, 305-243-2647

    Morgan Freret

    Recruiting

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

    Site Public Contact, 212-263-4432, cancertrials@nyulangone.org

    Jonathan T. Yang

    Recruiting

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

    Site Public Contact, CancerTrials@nyulangone.org

    Jonathan T. Yang

    Recruiting

  • New York Proton Center

    New York, New York, 10035

    Site Public Contact, 646-968-9031, ichoi@nyproton.com

    Arpit M. Chhabra

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

    Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu

    Jerry J. Jaboin

    Recruiting

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

    Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu

    Danielle Cunningham

    Recruiting

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

    Site Public Contact, 855-776-0015

    Eric Lehrer

    Recruiting

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

    Site Public Contact, 305-243-2647

    Morgan Freret

    Recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Site Public Contact, 855-776-0015

    Eric Lehrer

    Recruiting

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

    Site Public Contact, 888-424-2100, cancerinfo@hci.utah.edu

    Rachna Malani

    Recruiting

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

    Site Public Contact, rhabbaba@health.ucsd.edu

    Jona A. Hattangadi-Gluth

    Recruiting

  • California Protons Cancer Therapy Center

    San Diego, California, 92121

    Site Public Contact, 858-299-5982

    Jona A. Hattangadi-Gluth

    Recruiting

  • Memorial Hospital East

    Shiloh, Illinois, 62269

    Site Public Contact, 314-747-9912, dschwab@wustl.edu

    Nikhil Rammohan

    Recruiting

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

    Site Public Contact, 417-269-4520

    Jay W. Carlson

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Nikhil Rammohan

    Recruiting

  • Mercy Hospital South

    St Louis, Missouri, 63128

    Site Public Contact, 314-525-6042, Danielle.Werle@mercy.net

    Jay W. Carlson

    Recruiting

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Nikhil Rammohan

    Recruiting

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Nikhil Rammohan

    Recruiting

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Jana L. Fox

    Recruiting

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Jana L. Fox

    Recruiting

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

    Site Public Contact, 212-639-7592

    Yao Yu

    Recruiting

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

    Site Public Contact, 630-352-5360, Donald.Smith3@nm.org

    Vinai Gondi

    Recruiting

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

    Site Public Contact, 202-243-2373, jquiver1@jhmi.edu

    Carmen Kut

    Recruiting

Other trials in United States

About this study

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)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Computed Tomography, Involved-Field Radiation Therapy, Lumbar Puncture, Magnetic Resonance Imaging
Medical subject headings
Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Meningeal Carcinomatosis, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and CSF sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Involved-Field Radiation TherapyRadiation

    Also called IFRT, Involved field radiotherapy

    Undergo IFRT

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo LP

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Proton Beam Craniospinal IrradiationRadiation

    Also called Craniospinal Proton Beam Radiation Therapy, p-CSI, Proton Craniospinal Irradiation, Proton Craniospinal Radiation Therapy

    Undergo pCSI

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT06500481
Study groupRoleWhat they receive
Arm 1 (IFRT)Active comparatorPatients 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.
Receives: 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)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Central nervous system (CNS) progression-free survival (PFS)

    Will be based on modified ITT, including all randomized patients who have follow-up information. The analysis will be performed according to the treatment arm to which patients were randomized. Analysis for CNS-PFS will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a log-rank test. Statistical power will depend on the total CNS-PFS events accumulated at trial end. Additional analyses may consist of estimating the treatment hazard ratio via the Cox proportional hazards model accounting for prognostic covariates including randomization stratification factors evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying, and evaluating for potential treatment by prognostic covariate interactions.

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

  2. Time to CNS progression

    Analysis for time to CNS progression will involve comparing the rate of CNS progression in patients who receive pCSI to patients who receive IFRT. The cumulative incidence function (CIF) estimator will be used to estimate the median time to CNS progression in the presence of competing event of deaths in the two arms, separately. The Gray's test will be used to evaluate the difference in the distribution of CNS progression between treatment arms. These results will be interpreted in light of the competing deaths. The comparison of treatment effect on time to CNS progression will involve estimating the cause-specific hazard ratio (CHR) in a Cox proportional hazards model adjusting for patients and disease characteristics (e.g. stratification randomization factors).

    Measured: Randomization until CNS progression, assessed up to 3 years

  3. Time to radiation-induced CNS necrosis (TTRN)

    Analysis will involve comparing the rate of radiation necrosis in patients who receive pCSI to patients who receive IFRT. Death will be treated as a competing risk event in this analysis. The cumulative incidence function (CIF) estimator will be used to estimate the median time to radiation-induced CNS necrosis in the presence of competing event of deaths in the two arms, separately. The Gray's test will be used to evaluate the difference in the distribution of TTRN between treatment arms. These results will be interpreted in light of the competing deaths. The comparison of treatment effect on TTRN will involve estimating the CHR in a Cox proportional hazards model adjusting for patients and disease characteristics (e.g. stratification randomization factors).

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

  4. Incidence of treatment-related adverse events (AEs)

    Will be evaluated by comparative frequency summaries for all adverse event types between arms. AEs will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arms. Similarly, frequencies for specific potentially treatment related AEs where grade 3 or higher events are noted may be compared. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.

    Measured: Baseline to 30 days from end of radiation therapy

  5. Patient reported outcomes (PRO)

    Will be assessed using MD Anderson Symptom Inventory for Brain Tumors and MD Anderson Symptom Inventory for Spine Tumors. Data from these four subscales will be analyzed separately. For each subscale, scores from individual questions will be averaged to arrive at a subscale-specific score for each patient. The symptom severity scores, symptom interference scores, and brain tumor-specific and spine tumor-specific scores will be summarized at each assessment timepoint using descriptive statistics and visualized with box plots and series plots. Changes over time will also be assessed visually. The comparison of changes in quality of life between treatment arms will be conducted separately for each of these four subscales using mixed effects models.

    Measured: Baseline to 24 months post-radiation therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2024
  2. Study start4 Mar 2025
  3. Primary completion31 Jul 2028 (estimated)
  4. Study completion31 Jul 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
115 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06500481
Sponsor's protocol ID
NRG-BN014
Other IDs
NCI-2024-04895, NRG-BN014, NRG-BN014, U10CA180868
Status last verified
Aug 2026
First submitted
8 Jul 2024
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Computed Tomography and Involved-Field Radiation Therapy in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by NRG Oncology at 58 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: From randomization until death due to any cause, assessed up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06500481.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.

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