MRI Screening Versus SYMptom-directed Surveillance for Brain Metastases Among Patients With Triple Negative or HER2+ MBC (SYMPToM)

Routine MRI Screening Versus Symptom-directed Surveillance for Brain Metastases Among Patients With Triple Negative and HER2+ Metastatic Breast Cancer (MBC): A Single-centre Randomized Pilot Study

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.

Study Overview

• Status: Unknown
• Conditions: Breast Neoplasm; Triple Negative Breast Cancer; HER2-positive Breast Cancer; Brain Metastases
• Intervention / Treatment: Diagnostic test: MRI screening

Detailed Description

Please see trial details below.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katarzya J Jerzak, MD MSc FRCPC; Phone Number: 5248 4164806100; Email: katarzyna.jerzak@sunnybrook.ca
• Study Contact Backup: Name: Ellen Warner, MD FRCPC MSc; Phone Number: 4617 4164806100; Email: ellen.warner@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Odette Cancer Centre
      • Contact: Michael Julius, PhD; Phone Number: 4164806100; Email: michael.julius@sunnybrook.ca
      • Sub-Investigator: Ellen Warner, MD FRCPC MSc
      • Sub-Investigator: Arjun Sahgal, MD FRCPC
      • Sub-Investigator: Greg Stanisz, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18
2. Triple negative or HER2+ breast cancer (ASCO/CAP guidelines 2018)*
3. 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.
4. Diagnosis of metastatic disease within 12 weeks prior to study enrollment.
5. No symptoms of BrM or known asymptomatic BrM at study entry.

6. 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.

Exclusion Criteria:

1. 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.
2. Inability to provide informed consent. Notably participants who require translators are allowed to enroll.
3. Creatinine clearance <30 mL/min using the Cockcroft-Gault equation.
4. Established need for brain imaging apart from the breast cancer diagnosis (e.g surveillance for an aneurysm).
5. ECOG Performance status >2.
6. Pregnancy.
7. Grade 3+ allergy to Gadavist IV contrast (CTEP Adverse Event Reporting System).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRI screening; 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; 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.
No Intervention: Symptom-directed surveillance; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in the control arm who undergo imaging of the brain with CT or MRI.	This outcome is intended to assess the incidence of screening "contamination" in the control arm of the study.	12 months
Incidence of symptomatic brain metastases.	To be assessed in both study arms.	Baseline, 4-, 8- and 12-months.
Number of interventions used to treat brain metastases.	To be assessed in both study arms.	15 months
Size and location of BrM per patient.	To be assessed in both study arms.	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).	To be assessed in both study arms; 37 questions are rated from a scale of 0 to 4 (total score 0 to 185 where a lower score indicates better quality-of-life)	Baseline, 6 months and 15 months.
Overall quality-of-life (EORTC core quality of life questionnaire; EORTC QLQ-C30 version 3 tool).	To be assessed in both study arms; ; 30 questions are rated from a scale of 1 to 4 (total score 30 to 120 where a lower score indicates better quality-of-life)	Baseline, 6 months and 15 months.
Cancer-related anxiety (NCI PRO-CTCAE for anxiety).	To be assessed in both study arms.	Baseline, 6 months and 15 months.
Time to death due to any cause.	To be assessed in both study arms.	15 months.
Time to death due to neurologic progression.	To be assessed in both study arms.	15 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with changes in CEST imaging that are suggestive of brain metastases prior to confirmation on contrast-enhanced MRI imaging.	Exploratory outcome.	Baseline, 4-, 8- and 12-months.

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Harvard University
• Investigators: Principal Investigator: Katarzya J Jerzak, MD MSc FRCPC, University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2018
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 16, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 16, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: MRI; Quality of life; Screening; Surveillance
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 211-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD which does not include any patient identifiers will be considered but will require Research Ethics Board approval and appropriate legal contracts between collaborating institutions to ensure protection of patient data.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

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