CBF and NCF Changes With Brain Radiation

Use of Novel MRI Techniques Before and After Brain Radiotherapy With Parallel Assessments of Neurocognitive Function

This study will be a dual-arm prospective longitudinal cohort study for patients with brain metastases, at least one of which is appropriate for radiotherapy, to explore brain and cognitive changes following SRS or WBRT and evaluate the feasibility of a novel MRI protocol to identify potential radiological biomarkers of NCF decline.

Patients diagnosed with brain mets will be assigned to either Arm A or Arm B, depending on their treatment plan. Patients in Arm A will be treated with SRS. Patients in Arm B will be treated with WBRT.

Patients' neurocognitive function will be assessed before their radiation treatment and followed up for 2 years post treatment.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases; Neurocognitive Dysfunction
• Intervention / Treatment: Radiation: SRS and neurocognitive assessments; Radiation: WBRT and neurocognitive assessments

• Study Type: Observational
• Enrollment (Anticipated): 110

Contacts and Locations

• Study Contact: Name: David Shultz, MD; Phone Number: 2127 416-946-4501; Email: david.shultz@rmp.uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, L4W4C2
      • Recruiting
      • University Health Network
      • Contact: David Shultz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with brain metastases, at least one of which is appropriate for radiotherapy

Description

Inclusion Criteria:

• Patients with brain metastases will be included in this study. Patients with known malignancies but without brain metastases, or patients with primary brain tumors are not eligible for enrollment.
• MRI confirmed 1-10 lesions. Each lesion must not be intended for resection.
• No prior radiation therapy for brain tumours.
• For patients enrolled to arm B, ability to tolerate RespirAct. Based on studies in patients with severe cerebrovascular disease, an 8 - 16% drop-out rate at the time of the first exposure to RespirAct CVR testing is expected [9]. The fourth generation of this device has been associated with increased tolerability secondary to elimination of a physical rebreathing circuit replaced by a digital re-breath analog. This improvement is expected to achieve a drop-out rate significantly below 10%.
• Patients must have a GPA greater than or equal to 1.0.
• Patients must be able to provide informed consent. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Patients must have sufficient fluency in English and sufficient motor and visual functioning (corrected or assisted as required) to complete the NCF-A battery.
• Patients must be accessible for treatment, AE assessment and follow- up.
• Limit to KPS ≥ 70 for patients in arm B; no limit for arm A
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive. Women of childbearing potential will have a pregnancy test to determine eligibility.

Exclusion Criteria:

• Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
• Pregnant patients will be excluded from this study.
• Prior cranial radiotherapy
• Inability to complete MRI with contrast of the head, or a known allergy to gadolinium
• Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor.
• Patients with known malignancies but without brain metastases.

• Image Findings

  • Widespread definitive leptomeningeal metastasis
  • A brain metastasis that is located ≤ 2 mm of the optic chiasm
  • Evidence of midline shift
  • Fourth ventricular narrowing, concerning for hydrocephalus
• Patients who have undergone surgical resection of brain tumor are not eligible for enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm A; Patients in Arm A will be treated with stereotactic radiosurgery (SRS) which is a modern method of treating brain lesions that delivers a high amount of radiation to a small volume of the brain affected by a tumour; and is the standard of care for patients with a limited number of brain metastases.	Radiation: SRS and neurocognitive assessments; Patients will be assessed for cerebral blood flow and their neurocognitive function based on a series of neurocognitive tests and questionnaires.
Arm B.; Patients in Arm B will be treated with whole brain radiotherapy, due to the number of lesions in their brain.	Radiation: WBRT and neurocognitive assessments; Patients will be assessed for cerebral blood flow and their neurocognitive function based on a series of neurocognitive tests and questionnaires.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in neurocognitive function (NCF)	To characterize change in NCF from baseline (pre-SRS treatment), to 24 months following using the NCF-A Battery	Over 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic Radiation Toxicity	A diagnosis of symptomatic radiation toxicity will be based on a clinical onset of symptoms and radiological findings of radionecrosis at 3-24 months following radiosurgery, with or without pathological confirmation	3-24 months
Local Failure	Local failure will be defined as one of the following (follow-up MRI or CT brain scans will be compared to the prior MRI or CT brain scan): Increase of > 25% in the size of any lesion or a new, non- contiguous lesion developed outside the radiosurgical bed (in the brain or meninges). Radionecrosis will not be considered tumor progression.	up to 24 months
Distant Failure	Distant disease is considered to be new metastatic lesions in the brain or outside the brain following WBRT and SRS.	up to 24 months
Survival	Survival time will be measured from the date the patient is enrolled in this study to death, due to any cause	up to 24 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): July 30, 2018

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurocognitive Disorders; Central Nervous System Neoplasms; Nervous System Neoplasms; Cognition Disorders; Cognitive Dysfunction; Brain Neoplasms
• Other Study ID Numbers: 18-5106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No