Trial Title:
Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial
NCT ID:
NCT06500481
Condition:
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
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Lung Neoplasms
Neoplasms
Carcinoma, Non-Small-Cell Lung
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and CSF sample collection
Arm group label:
Arm 1 (IFRT)
Arm group label:
Arm 2 (pCSI)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Arm 1 (IFRT)
Arm group label:
Arm 2 (pCSI)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Radiation
Intervention name:
Involved-Field Radiation Therapy
Description:
Undergo IFRT
Arm group label:
Arm 1 (IFRT)
Other name:
IFRT
Other name:
Involved field radiotherapy
Intervention type:
Procedure
Intervention name:
Lumbar Puncture
Description:
Undergo LP
Arm group label:
Arm 1 (IFRT)
Arm group label:
Arm 2 (pCSI)
Other name:
LP
Other name:
Spinal Tap
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm 1 (IFRT)
Arm group label:
Arm 2 (pCSI)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Arm 1 (IFRT)
Arm group label:
Arm 2 (pCSI)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Radiation
Intervention name:
Proton Beam Craniospinal Irradiation
Description:
Undergo pCSI
Arm group label:
Arm 2 (pCSI)
Other name:
Craniospinal Proton Beam Radiation Therapy
Other name:
p-CSI
Other name:
Proton Craniospinal Irradiation
Other name:
Proton Craniospinal Radiation Therapy
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Arm 1 (IFRT)
Arm group label:
Arm 2 (pCSI)
Other name:
Quality of Life Assessment
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- PRIOR TO STEP 1 REGISTRATION
- Patients with pathologically (histologically or cytologically) proven diagnosis of
breast cancer or NSCLC. Patients must have systemic disease evaluation through
standard of care imaging for example CT chest/abdomen/pelvis or body PET/CT
- 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 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 who are 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
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
November 30, 2024
Completion date:
July 31, 2033
Lead sponsor:
Agency:
NRG Oncology
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
NRG Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06500481
