Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial
Recruiting · NCT06500481 · Interventional (participants receive a specific treatment) · Lead sponsor: NRG Oncology
View the official record on ClinicalTrials.gov →Interventions studied
Biospecimen CollectionComputed TomographyInvolved-Field Radiation TherapyLumbar PunctureMagnetic Resonance ImagingPositron Emission TomographyProton Beam Craniospinal IrradiationQuality-of-Life Assessment
What this trial is about
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.
Who can take part
Age range
18 Years and older
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 3
Study type
Interventional (participants receive a specific treatment)
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
Where it is running
58 locations listed across 17 US states.
- Mayo Clinic Hospital in Arizona - Phoenix, Arizona, United States
- University of Arkansas for Medical Sciences - Little Rock, Arkansas, United States
- UC San Diego Health System - Encinitas - Encinitas, California, United States
- UC San Diego Moores Cancer Center - La Jolla, California, United States
- UC San Diego Medical Center - Hillcrest - San Diego, California, United States
- California Protons Cancer Therapy Center - San Diego, California, United States
- Sibley Memorial Hospital - Washington D.C., District of Columbia, United States
- UM Sylvester Comprehensive Cancer Center at Aventura - Aventura, Florida, United States
- UM Sylvester Comprehensive Cancer Center at Coral Gables - Coral Gables, Florida, United States
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach - Deerfield Beach, Florida, United States
- UM Sylvester Comprehensive Cancer Center at Doral - Doral, Florida, United States
- University of Miami Miller School of Medicine-Sylvester Cancer Center - Miami, Florida, United States
- Miami Cancer Institute - Miami, Florida, United States
- UM Sylvester Comprehensive Cancer Center at Kendall - Miami, Florida, United States
- UM Sylvester Comprehensive Cancer Center at Plantation - Plantation, Florida, United States
- Alton Memorial Hospital - Alton, Illinois, United States
- Northwestern University - Chicago, Illinois, United States
- Northwestern Medicine Cancer Center Kishwaukee - DeKalb, Illinois, United States
- Northwestern Medicine Cancer Center Delnor - Geneva, Illinois, United States
- Memorial Hospital East - Shiloh, Illinois, United States
- Northwestern Medicine Cancer Center Warrenville - Warrenville, Illinois, United States
- University of Kansas Cancer Center - Kansas City, Kansas, United States
- University of Kansas Cancer Center-Overland Park - Overland Park, Kansas, United States
- Johns Hopkins University/Sidney Kimmel Cancer Center - Baltimore, Maryland, United States
- Wayne State University/Karmanos Cancer Institute - Detroit, Michigan, United States
- Weisberg Cancer Treatment Center - Farmington Hills, Michigan, United States
- McLaren Cancer Institute-Flint - Flint, Michigan, United States
- Karmanos Cancer Institute at McLaren Greater Lansing - Lansing, Michigan, United States
- Mayo Clinic in Rochester - Rochester, Minnesota, United States
- Siteman Cancer Center at Saint Peters Hospital - City of Saint Peters, Missouri, United States
- Siteman Cancer Center at West County Hospital - Creve Coeur, Missouri, United States
- University of Kansas Cancer Center - North - Kansas City, Missouri, United States
- University of Kansas Cancer Center - Lee's Summit - Lee's Summit, Missouri, United States
- Mercy Hospital Springfield - Springfield, Missouri, United States
- Washington University School of Medicine - St Louis, Missouri, United States
- Mercy Hospital South - St Louis, Missouri, United States
- Siteman Cancer Center-South County - St Louis, Missouri, United States
- Siteman Cancer Center at Christian Hospital - St Louis, Missouri, United States
- Memorial Sloan Kettering Basking Ridge - Basking Ridge, New Jersey, United States
- Memorial Sloan Kettering Monmouth - Middletown, New Jersey, United States
- Memorial Sloan Kettering Bergen - Montvale, New Jersey, United States
- NYU Langone Hospital - Brooklyn - Brooklyn, New York, United States
- Memorial Sloan Kettering Commack - Commack, New York, United States
- Memorial Sloan Kettering Westchester - Harrison, New York, United States
- NYU Langone Hospital - Long Island - Mineola, New York, United States
- Laura and Isaac Perlmutter Cancer Center at NYU Langone - New York, New York, United States
- New York Proton Center - New York, New York, United States
- Memorial Sloan Kettering Cancer Center - New York, New York, United States
- Montefiore Medical Center-Einstein Campus - The Bronx, New York, United States
- Montefiore Medical Center - Moses Campus - The Bronx, New York, United States
- Memorial Sloan Kettering Nassau - Uniondale, New York, United States
- Ohio State University Comprehensive Cancer Center - Columbus, Ohio, United States
- University of Oklahoma Health Sciences Center - Oklahoma City, Oklahoma, United States
- Huntsman Cancer Institute/University of Utah - Salt Lake City, Utah, United States
- Inova Alexandria Hospital - Alexandria, Virginia, United States
- Inova Schar Cancer Institute - Fairfax, Virginia, United States
- Inova Fair Oaks Hospital - Fairfax, Virginia, United States
- Inova Loudoun Hospital - Leesburg, Virginia, United States