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NCT Number: NCT06518057

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

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.

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Key information

Conditions

Anatomic Stage IV Breast Cancer AJCC v8 Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Central Nervous System Neoplasms Lung Diseases Lung Neoplasms Meningeal Carcinomatosis Meningeal Neoplasms Metastatic Breast Carcinoma Metastatic Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Leptomeninges Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Stage IV Lung Cancer AJCC v8 Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of California San Francisco, San Francisco, California, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Biospecimen Collection

Procedure

Undergo CSF sample collection

Other names: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Computed Tomography

Procedure

Undergo PET/CT and/or CT

Other names: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Electronic Health Record Review

Other

Ancillary studies

Lumbar Puncture

Procedure

Undergo lumbar puncture

Other names: LP, Spinal Tap

Magnetic Resonance Imaging

Procedure

Undergo MRI

Other names: 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

Positron Emission Tomography

Procedure

Undergo PET/CT

Other names: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Proton Beam Craniospinal Irradiation

Radiation

Undergo proton CSI

Other names: Craniospinal Proton Beam Radiation Therapy, p-CSI, Proton Craniospinal Irradiation, Proton Craniospinal Radiation Therapy

Survey Administration

Other

Ancillary studies

Volume Modulated Arc Therapy

Radiation

Undergo photon VMAT CSI

Other names: VMAT, Volumetric Modulated Arc Therapy (procedure)

Hippocampal-Avoidance Craniospinal Irradiation

Procedure

Undergo HA

Other names: Hippocampal-sparing Craniospinal Irradiation

Primary outcomes

  1. Central nervous system (CNS)-progression free survival (PFS)

    Time frame: Up to 12 months

    PFS is defined as time from craniospinal irradiation (CSI) to CNS disease progression or death. CNS-PFS will be summarized using Kaplan-Meier methodology. Median, 95% confidence interval (CI) and Kaplan-Meier plot will be provided. One-sample log-rank test will be used to test if the median CNS PFS of hippocampal avoidance in CSI for leptomeningeal metastases from breast cancer or non-small cell lung cancer (NSCLC) is significantly larger than the expected median CNS PFS with involved-field radiation therapy (IFRT), i.e., 2.5 months. P-value will be provided.

Secondary outcomes

  1. Number of adverse events associated with hippocampal avoidance craniospinal irradiation (HA-CSI)

    Time frame: Up to 12 months

    The analyses of the adverse events associated with HA-CSI will be descriptive in nature. Summary tables and listings will be provided for all reported adverse events (AEs).

  2. Neurocognitive function assessment

    Time frame: Up to 12 months

    Linear mixed models will be used to examine changes in neurocognitive domain (attention, executive functions, memory) performances from pre-RT baseline to 3, 6, and 12 months. Magnitude of change will be examined at each timepoint using standardized effect sizes (e.g., Cohen's d). For each timepoint, the study investigators will examine the proportion of individuals who demonstrate a reliable change in at least 2 (out of 10) test performances as compared to pre-RT baseline performances.

  3. Overall survival (OS)

    Time frame: Up to 12 months

    Comparison of OS between the study group and the historical cohort will be analyzed using stratified log-rank test. OS will be estimated and visualized using Kaplan-Meier methods.

Study contacts

Contact information is provided by the study sponsor or research team.

Lia M. Halasz

CONTACT

[email protected]

206-897-2121

Sponsors and collaborators

Lead sponsor

University of Washington

Other

Registry information

Official study title

A Multi-Center Phase 2 Study of Hippocampal Avoidance in Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumors

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jul 24, 2024
Registry last updated
Jun 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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