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

NCT ID: NCT06500481

Last Updated: 2026-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

115 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-04

Study Completion Date

2028-07-31

Brief Summary

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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

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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.

Conditions

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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 Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and CSF sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Involved-Field Radiation Therapy

Intervention Type RADIATION

Undergo IFRT

Lumbar Puncture

Intervention Type PROCEDURE

Undergo LP

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and CSF sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Lumbar Puncture

Intervention Type PROCEDURE

Undergo LP

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Proton Beam Craniospinal Irradiation

Intervention Type RADIATION

Undergo pCSI

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Interventions

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Biospecimen Collection

Undergo blood and CSF sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT or PET/CT

Intervention Type PROCEDURE

Involved-Field Radiation Therapy

Undergo IFRT

Intervention Type RADIATION

Lumbar Puncture

Undergo LP

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Proton Beam Craniospinal Irradiation

Undergo pCSI

Intervention Type RADIATION

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection 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 IFRT Involved field radiotherapy LP Spinal Tap 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 Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Craniospinal Proton Beam Radiation Therapy p-CSI Proton Craniospinal Irradiation Proton Craniospinal Radiation Therapy Quality of Life Assessment

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NRG Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan T Yang

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status RECRUITING

UC San Diego Health System - Encinitas

Encinitas, California, United States

Site Status RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status RECRUITING

UC San Diego Medical Center - Hillcrest

San Diego, California, United States

Site Status RECRUITING

California Protons Cancer Therapy Center

San Diego, California, United States

Site Status RECRUITING

Sibley Memorial Hospital

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

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, United States

Site Status RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status RECRUITING

Miami Cancer Institute

Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status RECRUITING

Alton Memorial Hospital

Alton, Illinois, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Site Status RECRUITING

Memorial Hospital East

Shiloh, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status RECRUITING

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

Site Status RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

Site Status RECRUITING

McLaren Cancer Institute-Flint

Flint, Michigan, United States

Site Status RECRUITING

Karmanos Cancer Institute at McLaren Greater Lansing

Lansing, Michigan, United States

Site Status RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status RECRUITING

University of Kansas Cancer Center - North

Kansas City, Missouri, United States

Site Status RECRUITING

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States

Site Status RECRUITING

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Mercy Hospital South

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status RECRUITING

NYU Langone Hospital - Brooklyn

Brooklyn, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, United States

Site Status RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status RECRUITING

New York Proton Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Site Status RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Inova Alexandria Hospital

Alexandria, Virginia, United States

Site Status RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status RECRUITING

Inova Fair Oaks Hospital

Fairfax, Virginia, United States

Site Status RECRUITING

Inova Loudoun Hospital

Leesburg, Virginia, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Site Public Contact

Role: primary

501-686-8274

Site Public Contact

Role: primary

760-536-7700

Site Public Contact

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858-822-5354

Site Public Contact

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858-299-5982

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202-243-2373

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954-461-2180

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305-243-2647

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305-243-2647

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305-243-2647

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786-596-2000

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305-243-2647

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305-243-2647

Site Public Contact

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618-463-7323

Site Public Contact

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312-695-1301

Site Public Contact

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630-352-5360

Site Public Contact

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630-352-5360

Site Public Contact

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314-747-9912

Site Public Contact

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630-352-5360

Site Public Contact

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913-588-3671

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913-588-3671

Site Public Contact

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410-955-8804

Site Public Contact

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313-576-9790

Site Public Contact

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313-576-9790

Site Public Contact

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313-576-9790

Site Public Contact

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313-576-9790

Site Public Contact

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855-776-0015

Site Public Contact

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800-600-3606

Site Public Contact

Role: primary

800-600-3606

Site Public Contact

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913-588-3671

Site Public Contact

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913-588-3671

Site Public Contact

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417-269-4520

Site Public Contact

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800-600-3606

Site Public Contact

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314-525-6042

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800-600-3606

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800-600-3606

Site Public Contact

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212-639-7592

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212-639-7592

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212-639-7592

Site Public Contact

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646-754-4624

Site Public Contact

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212-639-7592

Site Public Contact

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212-639-7592

Site Public Contact

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212-263-4432

Site Public Contact

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Site Public Contact

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646-968-9031

Site Public Contact

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212-639-7592

Site Public Contact

Role: primary

718-379-6866

Site Public Contact

Role: primary

718-379-6866

Site Public Contact

Role: primary

212-639-7592

Site Public Contact

Role: primary

800-293-5066

Site Public Contact

Role: primary

405-271-8777

Site Public Contact

Role: primary

888-424-2100

Site Public Contact

Role: primary

703-776-2580

Site Public Contact

Role: primary

703-720-5210

Site Public Contact

Role: primary

703-720-5210

Site Public Contact

Role: primary

703-858-6000

Other Identifiers

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NCI-2024-04895

Identifier Type: REGISTRY

Identifier Source: secondary_id

NRG-BN014

Identifier Type: OTHER

Identifier Source: secondary_id

NRG-BN014

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NRG-BN014

Identifier Type: -

Identifier Source: org_study_id

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