Hippocampal-Sparing Stereotactic Radiosurgery Treatment of Brain Metastases Using CyberKnife

Brain Metastases Clinical Trial

— HiSparCK  

Official title:

A Phase 2 Prospective Trial of Hippocampal-Sparing Stereotactic Radiosurgery Treatment of Brain Metastases Using CyberKnife

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05177185
• Other study ID #: 20200253-01H
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2022
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis
• Radiosurgery

Intervention

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).
• 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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

References & Publications (1)

Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, Bovi JA, Robinson C, Konski A, Khuntia D, Grosshans D, Benzinger TLS, Bruner D, Gilbert MR, Roberge D, Kundapur V, Devisetty K, Shah S, Usuki K, Anderson BM, Stea B, Yoon H, Li J, Laack NN, Kruser TJ, Chmura SJ, Shi W, Deshmukh S, Mehta MP, Kachnic LA; for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1;38(10):1019-1029. doi: 10.1200/JCO.19.02767. Epub 2020 Feb 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Neurocognitive Failure	Neurocognitive failure is defined as the first failure, defined as a neurocognitive decline in at least one of the following tests; Hopkins Verbal Learning Test for total recall, delayed recall and delayed recognition; Controlled oral word association; Trail making tests part A and B; Brief visuospatial memory test revised.	Baseline, 3 months, 6 months, 12 months (+/- 2 weeks)
Secondary	Rate of Neurocognitive Preservation	Neurocognitive failure is defined as the first failure, defined as a neurocognitive decline in at least one of the following tests; Hopkins Verbal Learning Test for total recall, delayed recall and delayed recognition; Controlled oral word association; Trail making tests part A and B; Brief visuospatial memory test revised.	Baseline, 3 months, 6 months, 12 months (+/- 2 weeks)
Secondary	Change from M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score	M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score is a 28-item multi-symptom patient-reported outcome that measures severity of symptoms experience by patients, 9 specific items for patients with brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Symptom Severity) is the average of the subscale items, given that a specified minimum numbers of items were completed.	Baseline, 3 months, 6 months, 12 months (+/- 2 weeks)
Secondary	Intracranial Progression-Free Survival	Intracranial progression-free survival time defined as time from registration to the date of progression in the brain or death from any cause. Overall survival rates are estimated by Kaplan-Meier method. Patients last known to be alive with be censored at date of last contact. Analysis will be planned after neurocognitive failure is reported.	Baseline, 3 months, 6 months, 12 months (+/- 2 weeks)
Secondary	Overall Survival	Overall survival time defined as time from registration to the date of death from any cause. Overall survival rates are estimated by Kaplan-Meier method. Patients last known to be alive with be censored at date of last contact. Analysis will be planned after neurocognitive failure is reported.	Baseline, 3 months, 6 months, 12 months (+/- 2 weeks)
Secondary	Number of Patients with Grade3+ Adverse Event	Adverse events will be graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to severity of adverse event; graded from 1 to 5. Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening/disabling, Grade 5 death related to adverse event	Baseline, 3 months, 6 months, 12 months (+/- 2 weeks)