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

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ClinicalTrials.gov Identifier: NCT03881605
Recruitment Status : Recruiting
First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Harvard University
Information provided by (Responsible Party):
Dr. Katarzyna Jerzak, Sunnybrook Health Sciences Centre

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.


Condition or disease Intervention/treatment Phase
Breast Neoplasm Brain Metastases Triple Negative Breast Cancer HER2-positive Breast Cancer Diagnostic Test: MRI screening Not Applicable

Detailed Description:
Please see trial details below.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled trial
Masking: None (Open Label)
Primary Purpose: Screening
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
Actual Study Start Date : November 8, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


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).



Primary Outcome Measures :
  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. [ Time Frame: 15 months. ]
    This outcome is intended to assess the feasibility of a future large, multi-center randomized trial.


Secondary Outcome Measures :
  1. Proportion of patients in the control arm who undergo imaging of the brain with CT or MRI. [ Time Frame: 12 months ]
    This outcome is intended to assess the incidence of screening "contamination" in the control arm of the study.

  2. Incidence of symptomatic brain metastases. [ Time Frame: Baseline, 4-, 8- and 12-months. ]
    To be assessed in both study arms.

  3. Number of interventions used to treat brain metastases. [ Time Frame: 15 months ]
    To be assessed in both study arms.

  4. Size and location of BrM per patient. [ Time Frame: At the time of diagnosis of brain metastases (from enrollment to 15 months) ]
    To be assessed in both study arms.

  5. Neurologic-specific quality-of-life (The Functional Assessment of Cancer Therapy-Brain; FACT-BR version 4 tool). [ Time Frame: Baseline, 6 months and 15 months. ]
    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)

  6. Overall quality-of-life (EORTC core quality of life questionnaire; EORTC QLQ-C30 version 3 tool). [ Time Frame: Baseline, 6 months and 15 months. ]
    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)

  7. Cancer-related anxiety (NCI PRO-CTCAE for anxiety). [ Time Frame: Baseline, 6 months and 15 months. ]
    To be assessed in both study arms.

  8. Time to death due to any cause. [ Time Frame: 15 months. ]
    To be assessed in both study arms.

  9. Time to death due to neurologic progression. [ Time Frame: 15 months. ]
    To be assessed in both study arms.


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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03881605


Contacts
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Contact: Katarzya J Jerzak, MD MSc FRCPC 4164806100 ext 5248 katarzyna.jerzak@sunnybrook.ca
Contact: Ellen Warner, MD FRCPC MSc 4164806100 ext 4617 ellen.warner@sunnybrook.ca

Locations
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Canada, Ontario
Sunnybrook Odette Cancer Centre Recruiting
Toronto, Ontario, Canada, M4N3M5
Contact: Michael Julius, PhD    4164806100    michael.julius@sunnybrook.ca   
Sub-Investigator: Ellen Warner, MD FRCPC MSc         
Sub-Investigator: Arjun Sahgal, MD FRCPC         
Sub-Investigator: Greg Stanisz, PhD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Harvard University
Investigators
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Principal Investigator: Katarzya J Jerzak, MD MSc FRCPC University of Toronto

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Responsible Party: Dr. Katarzyna Jerzak, Medical Oncologist and Clinician Investigator, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03881605     History of Changes
Other Study ID Numbers: 211-2018
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Katarzyna Jerzak, Sunnybrook Health Sciences Centre:
MRI
Screening
Quality of life
Surveillance
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases