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

Launched by NRG ONCOLOGY · Jul 8, 2024

Keywords

ClinConnect Summary

The RADIATE-LM trial is a clinical study that is comparing two types of radiation therapy for patients with certain types of advanced cancer, specifically breast cancer and non-small cell lung cancer, that has spread to the area around the brain and spinal cord (known as leptomeningeal metastasis). This condition can cause serious problems with the nervous system. The trial is looking at whether a newer approach called proton craniospinal irradiation (pCSI), which uses protons to target the entire area more precisely, is better than the usual method, known as involved-field radiation therapy (IFRT), which focuses on specific areas. Participants in this study may help researchers understand if pCSI can delay or prevent worsening of symptoms related to leptomeningeal metastasis.

To join this trial, participants must be at least 18 years old and have a confirmed diagnosis of breast cancer or non-small cell lung cancer with leptomeningeal metastasis. They should also be in good enough health to receive radiation therapy and meet certain other health criteria. If eligible, participants will receive either pCSI or IFRT and will be monitored for their symptoms and overall health. The trial is currently recruiting, and it offers an opportunity for patients to potentially receive a newer treatment while contributing to important research.

Gender

ALL

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