Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hippocampal-Sparing Stereotactic Radiosurgery Treatment of Brain Metastases Using CyberKnife (HiSparCK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05177185
Recruitment Status : Not yet recruiting
First Posted : January 4, 2022
Last Update Posted : February 16, 2022
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Brief 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.


Condition or disease Intervention/treatment Phase
Brain Metastases Radiosurgery Radiation: Hippocampal-sparing Radiation: Stereotactic radiosurgery Phase 2

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All patients will undergo hippocampal-sparing stereotactic radiosurgery
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Prospective Trial of Hippocampal-Sparing Stereotactic Radiosurgery Treatment of Brain Metastases Using CyberKnife
Estimated Study Start Date : April 1, 2022
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : December 30, 2024

Arm Intervention/treatment
Experimental: SRS with hippocampal-sparing
Stereotactic radiosurgery with hippocampal-sparing
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).
Other Names:
  • SRS
  • Stereotactic radiotherapy




Primary Outcome Measures :
  1. Time to Neurocognitive Failure [ Time Frame: Baseline, 3 months, 6 months, 12 months (+/- 2 weeks) ]
    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.


Secondary Outcome Measures :
  1. Rate of Neurocognitive Preservation [ Time Frame: Baseline, 3 months, 6 months, 12 months (+/- 2 weeks) ]
    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.

  2. Change from M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score [ Time Frame: Baseline, 3 months, 6 months, 12 months (+/- 2 weeks) ]
    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.

  3. Intracranial Progression-Free Survival [ Time Frame: Baseline, 3 months, 6 months, 12 months (+/- 2 weeks) ]
    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.

  4. Overall Survival [ Time Frame: Baseline, 3 months, 6 months, 12 months (+/- 2 weeks) ]
    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.

  5. Number of Patients with Grade3+ Adverse Event [ Time Frame: Baseline, 3 months, 6 months, 12 months (+/- 2 weeks) ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Publications:
Layout table for additonal information
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT05177185    
Other Study ID Numbers: 20200253-01H
First Posted: January 4, 2022    Key Record Dates
Last Update Posted: February 16, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We do not plan to make individual patient data available to other researchers

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ottawa Hospital Research Institute:
Hippocampal-sparing
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases