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)

Proton vs. Standard Radiation for Cancer Spread to Brain/Spine

NCT: NCT06500481 · Status: RECRUITING · Phase: Phase 3 · Sponsor: NRG Oncology · Started: 2025-03-04 · Est. Completion: 2028-07-31

Plain English Summary

Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial is a Phase 3 clinical trial sponsored by NRG Oncology studying 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. This trial tests a newer type of radiation therapy called proton therapy against standard radiation therapy for breast or lung cancer that has spread to the fluid around the brain and spinal cord. It is for patients with breast cancer or non-small cell lung cancer that has spread to the leptomeninges (the membranes surrounding the brain and spinal cord). Participation involves receiving either proton radiation or standard radiation therapy, along with regular medical check-ups, imaging scans, and possibly blood or spinal fluid tests. The alternative treatment is standard radiation therapy (involved-field radiotherapy) which is currently used for this condition. The trial aims to enroll 115 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18 or older with a confirmed diagnosis of breast cancer or non-small cell lung cancer that has spread to the leptomeninges can join. Patients must be able to receive radiation therapy and have a certain level of general health and organ function (e.g., blood counts, liver function). Patients cannot have had prior radiation to the spinal cord or treatment specifically for leptomeningeal metastasis. They also cannot be pregnant or nursing. This trial is studying 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, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients live after starting the trial, helping to understand if one radiation type offers a survival benefit over the other. The specific primary outcome measures are: Overall survival (OS) (From randomization until death due to any cause, assessed up to 3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to determine if proton radiation therapy is more effective than standard radiation in controlling cancer spread to the brain and spinal fluid, addressing a critical need for better tre As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets 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, where improved treatment options are needed.

Investor Insight

This Phase III trial, sponsored by NRG Oncology, targets a significant unmet need in advanced cancer care, with proton therapy representing a potentially more precise and less toxic treatment option, Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if proton therapy is suitable for your specific situation and how it differs from standard radiation. Understand the time commitment for radiation sessions, follow-up appointments, and any required tests. Be prepared for potential side effects and discuss any new symptoms or concerns with your medical team promptly. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Full 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 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

Trial Locations

Frequently Asked Questions

What is clinical trial NCT06500481?

NCT06500481 is a Phase 3 INTERVENTIONAL study titled "Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial." It is currently recruiting and is sponsored by NRG Oncology. The trial targets enrollment of 115 participants.

What conditions does NCT06500481 study?

This trial investigates treatments for 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. The primary condition under study is Anatomic Stage IV Breast Cancer AJCC v8.

What treatments are being tested in NCT06500481?

The interventions being studied include: Biospecimen Collection (PROCEDURE), Computed Tomography (PROCEDURE), Involved-Field Radiation Therapy (RADIATION), Lumbar Puncture (PROCEDURE), Magnetic Resonance Imaging (PROCEDURE). Undergo blood and CSF sample collection

What does Phase 3 mean for NCT06500481?

Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.

What is the current status of NCT06500481?

This trial is currently "Recruiting." It started on 2025-03-04. The estimated completion date is 2028-07-31.

Who is sponsoring NCT06500481?

NCT06500481 is sponsored by NRG Oncology. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT06500481?

The trial aims to enroll 115 participants. The trial is currently recruiting and accepting new participants.

How is NCT06500481 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs none masking.

What are the primary outcomes being measured in NCT06500481?

The primary outcome measures are: Overall survival (OS) (From randomization until death due to any cause, assessed up to 3 years). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06500481 being conducted?

This trial is being conducted at 20 sites, including Phoenix, Arizona; Little Rock, Arkansas; Encinitas, California; La Jolla, California and 16 more sites (United States).

Where can I find official information about NCT06500481?

The official record for NCT06500481 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06500481. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06500481 testing in simple terms?

This trial tests a newer type of radiation therapy called proton therapy against standard radiation therapy for breast or lung cancer that has spread to the fluid around the brain and spinal cord. It is for patients with breast cancer or non-small cell lung cancer that has spread to the leptomeninges (the membranes surrounding the brain and spinal cord).

Why is this trial significant?

This trial aims to determine if proton radiation therapy is more effective than standard radiation in controlling cancer spread to the brain and spinal fluid, addressing a critical need for better tre As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.

What are the potential risks of participating in NCT06500481?

Potential side effects of radiation therapy can include fatigue, skin irritation, nausea, and neurological symptoms like headaches or dizziness. Proton therapy, while potentially more targeted, may still carry risks of damage to healthy tissues, leading to long-term effects depending on the area treated. There is a risk of treatment-related adverse events, which will be closely monitored throughout the trial. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06500481?

Ask your doctor if proton therapy is suitable for your specific situation and how it differs from standard radiation. Understand the time commitment for radiation sessions, follow-up appointments, and any required tests. Be prepared for potential side effects and discuss any new symptoms or concerns with your medical team promptly. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06500481 signal from an investment perspective?

This Phase III trial, sponsored by NRG Oncology, targets a significant unmet need in advanced cancer care, with proton therapy representing a potentially more precise and less toxic treatment option, This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.

What happens if the treatment in this trial doesn't work?

Participation involves receiving either proton radiation or standard radiation therapy, along with regular medical check-ups, imaging scans, and possibly blood or spinal fluid tests. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.