CBF and NCF Changes With Brain Radiation

Study Purpose

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.

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.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

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.	NCT03606421
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.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Health Network, Toronto
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	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Neurocognitive Dysfunction, Brain Metastases

Arms & Interventions

Arms

: 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.

: Arm B.

Patients in Arm B will be treated with whole brain radiotherapy, due to the number of lesions in their brain.

Interventions

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.

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.