Proton vs Photon Radiation for Meningeal Carcinomatosis

Not currently recruiting at 9 trial locations

Overseen By T. Jonathan Yang, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Neurologic deficits, Extensive systemic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if proton craniospinal radiation therapy (proton CSI) is more effective than partial photon radiation in preventing the progression of leptomeningeal metastasis, a cancer spread to the brain and spine. Proton CSI covers the entire brain and spine, while partial photon radiation targets only symptomatic areas. The study also examines whether proton CSI improves symptoms and compares side effects between the two treatments. Individuals with solid tumor cancer that has spread to the brain or spine and are eligible for radiation therapy may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that proton craniospinal irradiation (CSI) is generally safe for treating cancer that spreads to the fluid around the brain and spine. Studies have found that patients tolerate proton CSI well, and it can effectively control the disease over the long term. Evidence also suggests it may improve survival rates. No major safety concerns have emerged, making proton CSI a promising option for those facing this type of cancer spread. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Proton Craniospinal Irradiation (CSI) for treating meningeal carcinomatosis because it offers a more precise form of radiation therapy compared to traditional photon radiation. Proton therapy can deliver high doses of radiation directly to the tumor while sparing surrounding healthy tissues, potentially reducing side effects and improving patient outcomes. This is particularly important for sensitive areas like the brain and spine. Additionally, this approach could lead to better control of cancer spread in the central nervous system, offering hope for patients with solid tumors, including those with non-small cell lung cancer (NSCLC) and breast cancer.

What evidence suggests that this trial's treatments could be effective for meningeal carcinomatosis?

This trial will compare Proton Craniospinal Irradiation (CSI) with Involved-field Photon Radiation Therapy for treating meningeal carcinomatosis. Studies have shown that proton CSI effectively manages central nervous system (CNS) disease in patients with leptomeningeal metastasis (LM), where cancer spreads to the layers surrounding the brain and spinal cord. Recent research found that proton CSI helped patients live longer compared to other treatments. Proton CSI targets the entire area where cancer might spread, potentially leading to better symptom control and slowing disease progression. In contrast, partial photon radiation therapy focuses only on symptomatic areas, which can relieve symptoms but might miss other affected areas. Overall, proton CSI might offer more comprehensive treatment for those with LM from solid tumors. ^{1 2 6 7 8}

Who Is on the Research Team?

Divya Yerramilli, MD, MBD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people of all ages with solid tumor cancers that have spread to the lining of the brain and spine. They must be able to perform daily activities reasonably well (KPS ≥ 60 or Lansky ≥ 60), have adequate bone marrow function, and not be pregnant. Participants should agree to use effective contraception and be candidates for radiation therapy.

Inclusion Criteria

My blood tests show normal levels of hemoglobin, neutrophils, and platelets.

My cancer has spread to the lining of my brain and spinal cord.

I am not pregnant and agree to use birth control during the study.

Exclusion Criteria

I've had radiation before where they now want to treat, and can't have more without risking harm.

Pregnant or lactating women

Patient with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive either proton craniospinal irradiation (proton CSI) or involved-field photon radiation therapy

2 weeks

10 visits (in-person)

Standard of Care Systemic Treatments

Participants receive standard of care systemic treatments for leptomeningeal metastases per physician choice

Follow-up

Participants are monitored for overall survival and CNS progression-free survival

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Involved-field Photon Radiation Therapy
• Proton Craniospinal Irradiation (CSI)

Trial Overview The study compares two types of radiation therapy: proton craniospinal irradiation (proton CSI) which targets the entire area around the brain and spinal fluid, versus partial photon radiation therapy that only treats symptomatic areas. The goal is to see which method better prevents worsening of cancer spread in these regions.

How Is the Trial Designed?

Group I: Standard of Care Experimental Treatment 3 Interventions

Involved field photon RT including WBRT and/or focal spine RT (30Gy in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice.

Group II: Proton CSI Followed by Standard of Care (Other Solid Tumors) Experimental Treatment 3 Interventions

(Exploratory arm) Patients with solid tumor malignancies other than NSCLC or breast cancer will be enrolled to the exploratory proton CSI arm (Arm C) and will not undergo randomization. Proton CSI (30Gy \[RBE\] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice.

Group III: Proton CSI Followed by Standard of Care (NSCLC & Breast) Experimental Treatment 3 Interventions

Proton CSI (30Gy \[RBE\] in 10 fractions) followed by standard of care systemic treatments for leptomeningeal metastases per physician choice.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Fred Hutchinson Cancer Center

Collaborator

Trials

583

Recruited

1,341,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7850116/

Clinical trial of proton craniospinal irradiation for ... In addition, we found that CSI may be effective in achieving durable CNS disease control in patients with LM from solid tumors. The majority of ...

2. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00205-1/fulltext

Radiation Therapy in the Management of Leptomeningeal ... Radiation therapy (RT) is an essential tool in the management of LMD, and a recent randomized trial demonstrated a survival benefit for proton craniospinal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9671756/

Randomized Phase II Trial of Proton Craniospinal Irradiation ... Craniospinal irradiation (CSI), conversely, treats the whole leptomeningeal compartment and may therefore achieve superior symptom and disease ...

4. practicalradonc.org practicalradonc.org/article/S1879-8500(25)00172-9/abstract

Current Status of Proton Craniospinal Irradiation for Solid ... While IFRT offers effective symptom control, it is often short-term, as local out-of-field failure remains common, with no impact on the natural ...

5. academic.oup.com academic.oup.com/jrr/article/65/5/667/7734878

Craniospinal irradiation for leptomeningeal metastasis of solid ... We conducted a study to examine the treatment outcomes and prognostic factors for patients who underwent craniospinal irradiation (CSI) for leptomeningeal ...

6. mdpi.com mdpi.com/2072-6694/17/6/1046

Proton Craniospinal Irradiation for Patients with Solid ... Conclusions: pCSI is a safe and feasible treatment option for real-world patients with LMD, including those previously treated with radiotherapy to the spine.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0360301621009548

Long-Term Outcomes of a Prospective Clinical Trial ... We reported that pCSI is a safe treatment for patients with solid tumor LM. In this analysis, we demonstrated durable disease control and prolonged survival in ...

8. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-025-02618-7

Early experience with proton craniospinal irradiation in ... Recent data suggest proton craniospinal irradiation (pCSI) to be a promising treatment option, potentially prolonging progression-free survival (PFS) and ...