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)

Cancer Categories

Breast,Lung

Karmanos Trial ID

NRG-BN014

NCT ID

NCT06500481

Age Group

Adult

Scope

National

Phase

Phase III

Principal Investigator

Brian
Yeh, M.D., Ph.D.
Oncology - Radiation View Profile

Objective:

Primary Objective:

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:

To compare central nervous system progression-free survival (CNS PFS) between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.
To compare time to CNS progression between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.
To compare CNS PFS between pCSI and IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis, as evaluated by central review of imaging.
To compare the rate of radiation-induced central nervous system necrosis between pCSI vs. IFRT in patients with breast cancer or NSCLC leptomeningeal metastasis.
To characterize treatment-related adverse events using CTCAE v5.0.
To compare patient-reported outcomes (Symptoms Severity subscale per MDASI-BT and MDASI-SP) in patients with breast cancer or non-small cell lung cancer leptomeningeal metastasis

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Eligibility

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

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at McLaren Flint

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Flint, MI 48532
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Phone: 810-342-3800

Karmanos Cancer Institute at McLaren Greater Lansing - Medical Oncology and Hematology

3520 Forest Rd.
Lansing, MI 48910
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Phone: 517-975-9500

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices