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)

Status: Recruiting
Location: See all (56) locations...
Intervention Type: Other, Procedure, Radiation
Study Type: Interventional
Study Phase: Phase 3
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
RECRUITING
Little Rock
California
UC San Diego Health System - Encinitas
RECRUITING
Encinitas
UC San Diego Moores Cancer Center
RECRUITING
La Jolla
California Protons Cancer Therapy Center
RECRUITING
San Diego
UC San Diego Medical Center - Hillcrest
RECRUITING
San Diego
Washington, D.c.
Sibley Memorial Hospital
RECRUITING
Washington D.c.
Florida
UM Sylvester Comprehensive Cancer Center at Aventura
RECRUITING
Aventura
UM Sylvester Comprehensive Cancer Center at Coral Gables
RECRUITING
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
RECRUITING
Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Doral
RECRUITING
Doral
Miami Cancer Institute
RECRUITING
Miami
UM Sylvester Comprehensive Cancer Center at Kendall
RECRUITING
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
UM Sylvester Comprehensive Cancer Center at Plantation
RECRUITING
Plantation
Illinois
Alton Memorial Hospital
RECRUITING
Alton
Northwestern University
RECRUITING
Chicago
Northwestern Medicine Cancer Center Kishwaukee
RECRUITING
Dekalb
Northwestern Medicine Cancer Center Delnor
RECRUITING
Geneva
Memorial Hospital East
RECRUITING
Shiloh
Northwestern Medicine Cancer Center Warrenville
RECRUITING
Warrenville
Kansas
University of Kansas Cancer Center
RECRUITING
Kansas City
University of Kansas Cancer Center-Overland Park
RECRUITING
Overland Park
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Michigan
Wayne State University/Karmanos Cancer Institute
RECRUITING
Detroit
Weisberg Cancer Treatment Center
RECRUITING
Farmington Hills
McLaren Cancer Institute-Flint
RECRUITING
Flint
Karmanos Cancer Institute at McLaren Greater Lansing
RECRUITING
Lansing
Minnesota
Mayo Clinic in Rochester
RECRUITING
Rochester
Missouri
Siteman Cancer Center at Saint Peters Hospital
RECRUITING
City Of Saint Peters
Siteman Cancer Center at West County Hospital
RECRUITING
Creve Coeur
University of Kansas Cancer Center - North
RECRUITING
Kansas City
University of Kansas Cancer Center - Lee's Summit
RECRUITING
Lee's Summit
Mercy Hospital Springfield
RECRUITING
Springfield
Mercy Hospital South
RECRUITING
St Louis
Siteman Cancer Center at Christian Hospital
RECRUITING
St Louis
Siteman Cancer Center-South County
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
New Jersey
Memorial Sloan Kettering Basking Ridge
RECRUITING
Basking Ridge
Memorial Sloan Kettering Monmouth
RECRUITING
Middletown
Memorial Sloan Kettering Bergen
RECRUITING
Montvale
New York
Memorial Sloan Kettering Commack
RECRUITING
Commack
Memorial Sloan Kettering Westchester
RECRUITING
Harrison
NYU Langone Hospital - Long Island
RECRUITING
Mineola
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
New York Proton Center
RECRUITING
New York
Montefiore Medical Center - Moses Campus
RECRUITING
The Bronx
Montefiore Medical Center-Einstein Campus
RECRUITING
The Bronx
Memorial Sloan Kettering Nassau
RECRUITING
Uniondale
Ohio
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Virginia
Inova Alexandria Hospital
RECRUITING
Alexandria
Inova Fair Oaks Hospital
RECRUITING
Fairfax
Inova Schar Cancer Institute
RECRUITING
Fairfax
Inova Loudoun Hospital
RECRUITING
Leesburg
Time Frame
Start Date: 2025-03-04
Estimated Completion Date: 2028-07-31
Participants
Target number of participants: 115
Treatments
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.
Sponsors
Leads: NRG Oncology

This content was sourced from clinicaltrials.gov