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

University of Washington

Status and phase

Enrolling

Phase 2

Conditions

Anatomic Stage IV Breast Cancer AJCC v8

Metastatic Breast Carcinoma

Metastatic Lung Non-Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Metastatic Malignant Neoplasm in the Leptomeninges

Treatments

Procedure: Biospecimen Collection

Other: Survey Administration

Procedure: Lumbar Puncture

Procedure: Magnetic Resonance Imaging

Procedure: Computed Tomography

Procedure: Positron Emission Tomography

Radiation: Proton Beam Craniospinal Irradiation

Radiation: Volume Modulated Arc Therapy

Procedure: Hippocampal-Avoidance Craniospinal Irradiation

Other: Electronic Health Record Review

Study type

Interventional

Funder types

Other

Identifiers

NCT06518057

RG1124476

FHIRB0020569 (Other Identifier)

NCI-2024-05661 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

22 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

22 participants in 1 patient group

Treatment (Proton or Photon VMAT CSI)

Experimental group

Description:

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.

Treatment: