Clinical trial NCT03881605: MRI Screening Versus SYMptom-directed Surveillance for Brain Metastases Among Patients with Triple Negative or HER2+ MBC
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Neoplasm
Brain Metastases
Triple Negative Breast Cancer
HER2-positive Breast Cancer
Keywords: MRI
Screening
Quality of life
Surveillance
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Harvard University
First posted: 2019-03-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: SCREENING

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.

Detailed description: Please see trial details below.

Eligibility criteria: 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).

Primary outcomes:
measure: 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.
timeFrame: 15 months.
Secondary outcomes:
measure: Proportion of patients in the control arm who undergo imaging of the brain with CT or MRI.
timeFrame: 12 months
measure: Incidence of symptomatic brain metastases.
timeFrame: Baseline, 4-, 8- and 12-months.
measure: Number of interventions used to treat brain metastases.
timeFrame: 15 months
measure: Size and location of BrM per patient.
timeFrame: At the time of diagnosis of brain metastases (from enrollment to 15 months)
measure: Neurologic-specific quality-of-life (The Functional Assessment of Cancer Therapy-Brain; FACT-BR version 4 tool).
timeFrame: Baseline, 6 months and 15 months.
measure: Overall quality-of-life (EORTC core quality of life questionnaire; EORTC QLQ-C30 version 3 tool).
timeFrame: Baseline, 6 months and 15 months.
measure: Cancer-related anxiety (NCI PRO-CTCAE for anxiety).
timeFrame: Baseline, 6 months and 15 months.
measure: Time to death due to any cause.
timeFrame: 15 months.
measure: Time to death due to neurologic progression.
timeFrame: 15 months.
Other outcomes:
measure: Proportion of patients with changes in CEST imaging that are suggestive of brain metastases prior to confirmation on contrast-enhanced MRI imaging.
timeFrame: Baseline, 4-, 8- and 12-months.
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
Study officials:
affiliation: University of Toronto
name: Katarzya J Jerzak, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References: