Hippocampal-Sparing Stereotactic Radiosurgery Treatment of Brain Metastases Using CyberKnife

Study Purpose

This phase II clinical trial involves the use of hippocampal-sparing together with stereotactic radiosurgery (SRS) for the treatment of brain metastases. The standard of care in the treatment of brain metastases is cranial radiation, but this can be associated with significant neurocognitive sequelae, including reduced verbal memory, spatial memory, attention and problem solving. This can be minimized with the use of SRS, rather than whole brain radiotherapy (WBRT). Additionally, some of the neurotoxicity has been linked to damage in neural progenitor cells contained within the hippocampus. A recent phase III clinical trial has demonstrated reduced neurocognitive decline with use of hippocampal-sparing techniques in WBRT. This trial aims to see if this can be further improved by combining SRS and hippocampal-sparing.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 18 years of age or older.

- Either gender.

- Patients must provide informed consent prior to registration.

- Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy.

- Brain metastase(s) outside a 5-mm margin around either hippocampus.

- Brain metastase(s) must be visible on contrast-enhanced magnetic resonance imaging (MRI); an allowed exception for patients who had undergone radiosurgery or surgical resection and are planning adjuvant radiotherapy do not have to have visible disease.

- Patients must have a gadolinium contrast-enhanced three-dimensional MRI scan, whether diagnostic or a MR simulation scan.

- Karnofsky performance status of >= 70 or ECOG >= 2.

- Patients may have had prior therapy for brain metastasis, including radiosurgery, as long as with hippocampal-sparing, and surgical resection; patients must have completed prior therapy (no specific time lapse between prior treatment and this treatment)
Exclusion Criteria:
- Prior external beam radiation therapy to the brain or whole brain radiation therapy, unless radiosurgery with hippocampal-sparing.

- Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt.

- Patients with definitive leptomeningeal metastases.

- Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies.

- Contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05177185
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Ottawa Hospital Research Institute
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Metastases, Radiosurgery

Additional Details

Primary objective: To determine the rate of neurocognitive failure with hippocampal-sparing stereotactic radiosurgery compared to neurocognitive failures rates with hippocampal-sparing whole brain radiotherapy (using NRG-CC001 with the same population as our comparison), assessed at baseline and at months 3, 6 and 12 (+/- 2 weeks), and with failure defined as any decline in at least one of the following tests (of note, we will be using alternate forms to avoid practice effects): Hopkins Verbal Learning Test for total recall, delayed recall and delayed recognition, Controlled oral word association, Trail making tests parts A and B, Brief visuospatial memory test-revised. Secondary objectives: (I) To determine if hippocampal-sparing preserves neurocognitive function, assessed at baseline and months 3, 6 and 12 (+/- 2 weeks), and defined as decline in at least one of the following tests (of note, we will be using alternate forms to avoid practice effects): Hopkins Verbal Learning Test for total recall, delayed recall and delayed recognition, Controlled oral word association, Trail making tests parts A and B, Brief visuospatial memory test-revised. (II) To determine the incidence of adverse events up to 12 months post-treatment, as measured by common terminology criteria for adverse events (CTCAE v3.0) (III) Quality of life As measured using MD Anderson Symptom Inventory for Brain tumor (MDASI-BT)'s four subscales: symptom severity, symptom interference, neurologic failure and cognitive factor score; and individual items (fatigue, neurologic factor items and cognitive factor items). (III) Oncologic outcomes will also be assessed at surveillance every 3 months, as is standard of care; time to intracranial progression, overall survival. These will be estimated using Kaplan-Meier method.

Arms & Interventions

Arms

Experimental: SRS with hippocampal-sparing

Stereotactic radiosurgery with hippocampal-sparing

Interventions

Radiation: - Hippocampal-sparing

Dose constraint placed on hippocampi to minimize dose to hippocampi, while maintaining target coverage (at least 98% of brain metastasis volume must receive 100% of prescription dose).

Radiation: - Stereotactic radiosurgery

Stereotactic radiosurgery (SRS) with prescription dose determined based on size of brain metastasis; 21 or 24 Gy in a single fraction if less than or equal to 20 mm, 18Gy in a single fraction in 21 - 30 mm, 15 Gy in a single fraction or 30 Gy in 5 fractions if 31 - 40 mm (physician discretion).

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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