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

Purpose

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.

Conditions

  • 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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 an effective contraceptive method

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Procedure: Biospecimen Collection
    Undergo CSF sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Procedure: Computed Tomography
    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
  • Other: Electronic Health Record Review
    Ancillary studies
  • Procedure: Lumbar Puncture
    Undergo lumbar puncture
    Other names:
    • LP
    • Spinal Tap
  • Procedure: Magnetic Resonance Imaging
    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
  • Procedure: Positron Emission Tomography
    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
  • Radiation: Proton Beam Craniospinal Irradiation
    Undergo proton CSI
    Other names:
    • Craniospinal Proton Beam Radiation Therapy
    • p-CSI
    • Proton Craniospinal Irradiation
    • Proton Craniospinal Radiation Therapy
  • Other: Survey Administration
    Ancillary studies
  • Radiation: Volume Modulated Arc Therapy
    Undergo photon VMAT CSI
    Other names:
    • VMAT
    • Volumetric Modulated Arc Therapy (procedure)
  • Procedure: Hippocampal-Avoidance Craniospinal Irradiation
    Undergo HA
    Other names:
    • Hippocampal-sparing Craniospinal Irradiation

Recruiting Locations

Fred Hutch/University of Washington Cancer Consortium
Seattle 5809844, Washington 5815135 98109
Contact:
Lia M. Halasz
206-897-2121
lhalasz@uw.edu

More Details

Status
Recruiting
Sponsor
University of Washington

Study Contact

Lia M. Halasz
206-897-2121
lhalasz@uw.edu

Detailed 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.