MRI Screening Versus SYMptom-directed Surveillance for Brain Metastases Among Patients with Triple Negative or HER2+ MBC

NCT03881605 | Active Not Recruiting

• 1 other identifier: 211-2018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, 50 women with either HER2+ or triple negative metastatic breast cancer but no known brain metastases will be recruited at the Sunnybrook Odette Cancer Centre. They will be randomized to undergo either routine MRI screening of their brain every 4 months for 1 year or standard-of-care (MRI only if symptoms of brain metastases develop). Patients will complete questionnaires about quality of life and cancer-related anxiety throughout the study. To determine why some cancers spread to the brain and others do not, blood samples will be collected to analyze the genetic makeup of patients' breast cancers. Finally, a novel MRI imaging technique that detects abnormal metabolism in the brain will be used to help detect brain metastases even earlier than the standard MRI. If results are promising, we will conduct a large multi-centre randomized trial to determine whether screening for brain metastases can help them live longer with improved quality of life.

Conditions

Breast Neoplasm; Brain Metastases; Triple Negative Breast Cancer; HER2-positive Breast Cancer

Keywords

MRI; Screening; Quality of life; Surveillance

Outcome Measures

Primary Outcomes (1)

• Proportion of eligible patients at the Sunnybrook Odette Cancer Centre (SOCC) who i) agree to enroll in the proposed randomized phase II pilot study, and ii) complete the study protocol.

  This outcome is intended to assess the feasibility of a future large, multi-center randomized trial.

  15 months.

Secondary Outcomes (9)

• Proportion of patients in the control arm who undergo imaging of the brain with CT or MRI.

  12 months

• Incidence of symptomatic brain metastases.

  Baseline, 4-, 8- and 12-months.

• Number of interventions used to treat brain metastases.

  15 months

• Size and location of BrM per patient.

  At the time of diagnosis of brain metastases (from enrollment to 15 months)

• Neurologic-specific quality-of-life (The Functional Assessment of Cancer Therapy-Brain; FACT-BR version 4 tool).

  Baseline, 6 months and 15 months.

Other Outcomes (1)

• Proportion of patients with changes in CEST imaging that are suggestive of brain metastases prior to confirmation on contrast-enhanced MRI imaging.

  Baseline, 4-, 8- and 12-months.

Study Arms (2)

MRI screening

EXPERIMENTAL

Contrast-enhanced MRI and Chemical Exchange Saturation Transfer (CEST) MRI of the brain at baseline, 4 months, 8 months and 12 months.

Diagnostic Test: MRI screening

Symptom-directed surveillance

NO INTERVENTION

Imaging of the brain will take place only if patients develop symptoms that are suggestive of brain metastases (e.g. headaches, vision changes, gait instability).

Interventions

MRI screening DIAGNOSTIC_TEST

A standard contrast-enhanced MRI and Chemical Exchange Saturation Transfer (CEST) MRI of the brain will be performed at baseline, 4 months, 8 months and 12 months.

MRI screening

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18
• Triple negative or HER2+ breast cancer (ASCO/CAP guidelines 2018)\*
• MBC, as defined as distant disease outside of the breast and local/regional lymph nodes. Physicians' clinical judgment will be used to determine the possible need for biopsy in confirming a MBC diagnosis. However, biopsy of a metastatic site is not required for pathologic confirmation of stage IV disease.
• Diagnosis of metastatic disease within 12 weeks prior to study enrollment.
• No symptoms of BrM or known asymptomatic BrM at study entry.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may participate.
• This will generally be based on the primary cancer but in the event that a metastatic site is biopsied eligibility will be based on the ER, PR and HER2 profile of the metastasis.

You may not qualify if:

• Inability to participate in an MRI screening program as determined by the patient and/or physician. This may be on the basis of severe claustrophobia, performance status that limits additional testing, or a metal foreign body that would prevent MRI imaging.
• Inability to provide informed consent. Notably participants who require translators are allowed to enroll.
• Creatinine clearance \<30 mL/min using the Cockcroft-Gault equation.
• Established need for brain imaging apart from the breast cancer diagnosis (e.g surveillance for an aneurysm).
• ECOG Performance status \>2.
• Pregnancy.
• Grade 3+ allergy to Gadavist IV contrast (CTEP Adverse Event Reporting System).

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Harvard University: collaborator

Study Sites (1)

Sunnybrook Odette Cancer Centre

Toronto, Ontario, M4N3M5, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Katarzya J Jerzak, MD MSc FRCPC

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist and Clinician Investigator

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 19, 2019
• Study Start: November 8, 2018
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The study documents (protocol, statistical analysis plan and informed consent form) can be made available at any time. Data may be available after study completion.
• Access Criteria: Research Ethics Board approval and appropriate legal contracts between collaborating institutions will be required prior to data-sharing to ensure protection of patient data.

Locations

CA (1)