Hippocampal Avoidance in Craniospinal Irradiation for the Treatment of Leptomeningeal Metastases From Breast Cancer or Non-small Cell Lung Cancer

NCT ID: NCT06518057

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-03

Study Completion Date

2027-12-30

Brief Summary

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This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.

Detailed Description

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OUTLINE:

Patients undergo proton or photon VMAT CSI with HA over approximately 45 minutes once daily (QD) for 10 days (Monday-Friday) in the absence of unacceptable toxicity. Patients may also undergo computed tomography (CT) or positron emission tomography (PET)/CT during screening. Additionally, patients will undergo additional CT for radiation planning during screening and magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo lumbar puncture (LP) or alternative methods for cerebral spinal fluid (CSF) collection at the discretion of the treating physician and principal investigator throughout the study.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and then at the time of CNS disease progression, up to 1 year.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (Proton or Photon VMAT CSI)

Patients undergo proton or photon VMAT CSI with HA over approximately 45 minutes once daily (QD) for 10 days (Monday-Friday) in the absence of unacceptable toxicity. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT during screening. Additionally, patients undergo additional CT for radiation planning during screening and magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo lumbar puncture (LP) or alternative methods for cerebral spinal fluid (CSF) collection at the discretion of the treating physician and principal investigator throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo CSF sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT and/or CT

Electronic Health Record Review

Intervention Type OTHER

Ancillary studies

Lumbar Puncture

Intervention Type PROCEDURE

Undergo lumbar puncture

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Proton Beam Craniospinal Irradiation

Intervention Type RADIATION

Undergo proton CSI

Survey Administration

Intervention Type OTHER

Ancillary studies

Volume Modulated Arc Therapy

Intervention Type RADIATION

Undergo photon VMAT CSI

Hippocampal-Avoidance Craniospinal Irradiation

Intervention Type PROCEDURE

Undergo HA

Interventions

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Biospecimen Collection

Undergo CSF sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo PET/CT and/or CT

Intervention Type PROCEDURE

Electronic Health Record Review

Ancillary studies

Intervention Type OTHER

Lumbar Puncture

Undergo lumbar puncture

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Proton Beam Craniospinal Irradiation

Undergo proton CSI

Intervention Type RADIATION

Survey Administration

Ancillary studies

Intervention Type OTHER

Volume Modulated Arc Therapy

Undergo photon VMAT CSI

Intervention Type RADIATION

Hippocampal-Avoidance Craniospinal Irradiation

Undergo HA

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography LP Spinal Tap Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Craniospinal Proton Beam Radiation Therapy p-CSI Proton Craniospinal Irradiation Proton Craniospinal Radiation Therapy VMAT Volumetric Modulated Arc Therapy (procedure) Hippocampal-sparing Craniospinal Irradiation

Eligibility Criteria

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Inclusion Criteria

* Patients with breast cancer or NSCLC malignancies with leptomeningeal metastases established radiographically and/or through CSF cytology
* Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastases
* Patients ≥ 18 years old
* Karnofsky performance status (KPS) ≥ 60 or Eastern Cooperative Oncology Group (ECOG) ≥ 2
* The patient is able to provide informed consent
* Hemoglobin \> 8 g/dL
* Absolute neutrophil count \> 1,000/mm
* Platelet count \> 100,000/mm
* Participants born female at birth must either be of non-reproductive potential (i.e. post-menopausal by history \[≥ 60 years old, or with no menses for \> 1 year without an alternative medical cause\], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum /urine pregnancy test within 3 weeks prior to starting radiation therapy (RT)
* Patients with reproductive potential must agree to practice two highly effective contraceptive methods

Exclusion Criteria

* Patients with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy
* Patients with extensive systemic disease and without reasonable systemic treatment options
* Patients who are unable to undergo MRI brain and spine with gadolinium contrast
* Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances
* Gross ventricular disease
* Brain metastases within 5 mm of the hippocampal contours not previously treated
* Pregnant or lactating women
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lia M. Halasz

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lia M. Halasz

Role: CONTACT

206-897-2121

Facility Contacts

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Lia M. Halasz

Role: primary

206-897-2121

Other Identifiers

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NCI-2024-05661

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020569

Identifier Type: OTHER

Identifier Source: secondary_id

RG1124476

Identifier Type: -

Identifier Source: org_study_id

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