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

Primary Purpose

Breast Neoplasm, Brain Metastases, Triple Negative Breast Cancer

Status

Unknown status

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

MRI screening

About this trial

This is an interventional screening trial for Breast Neoplasm focused on measuring MRI, Screening, Quality of life, Surveillance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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).

Sites / Locations

Sunnybrook Odette Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

MRI screening

Symptom-directed surveillance

Arm Description

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

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Incidence of symptomatic brain metastases.

To be assessed in both study arms.

Number of interventions used to treat brain metastases.

To be assessed in both study arms.

Size and location of BrM per patient.

To be assessed in both study arms.

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)

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)

Cancer-related anxiety (NCI PRO-CTCAE for anxiety).

To be assessed in both study arms.

Time to death due to any cause.

To be assessed in both study arms.

Time to death due to neurologic progression.

To be assessed in both study arms.

Full Information

NCT ID

NCT03881605

First Posted

March 14, 2019

Last Updated

March 16, 2019

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Harvard University

1. Study Identification

Unique Protocol Identification Number

NCT03881605

Brief Title

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

Acronym

SYMPToM

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

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Unknown status

Study Start Date

November 8, 2018 (Actual)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Harvard University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

MRI, Screening, Quality of life, Surveillance

7. Study Design

Primary Purpose

Screening

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Randomized controlled trial

Masking

None (Open Label)

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

MRI screening

Arm Type

Experimental

Arm Description

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

Arm Title

Symptom-directed surveillance

Arm Type

No Intervention

Arm Description

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).

Intervention Type

Diagnostic Test

Intervention Name(s)

MRI screening

Intervention Description

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.

Primary Outcome Measure Information:

Title

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.

Description

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

Time Frame

15 months.

Secondary Outcome Measure Information:

Title

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

Description

This outcome is intended to assess the incidence of screening "contamination" in the control arm of the study.

Time Frame

12 months

Title

Incidence of symptomatic brain metastases.

Description

To be assessed in both study arms.

Time Frame

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

Title

Number of interventions used to treat brain metastases.

Description

To be assessed in both study arms.

Time Frame

15 months

Title

Size and location of BrM per patient.

Description

To be assessed in both study arms.

Time Frame

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

Title

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

Description

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)

Time Frame

Baseline, 6 months and 15 months.

Title

Overall quality-of-life (EORTC core quality of life questionnaire; EORTC QLQ-C30 version 3 tool).

Description

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)

Time Frame

Baseline, 6 months and 15 months.

Title

Cancer-related anxiety (NCI PRO-CTCAE for anxiety).

Description

To be assessed in both study arms.

Time Frame

Baseline, 6 months and 15 months.

Title

Time to death due to any cause.

Description

To be assessed in both study arms.

Time Frame

15 months.

Title

Time to death due to neurologic progression.

Description

To be assessed in both study arms.

Time Frame

15 months.

Other Pre-specified Outcome Measures:

Title

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

Description

Exploratory outcome.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Katarzya J Jerzak, MD MSc FRCPC

Phone

4164806100

Ext

5248

katarzyna.jerzak@sunnybrook.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Ellen Warner, MD FRCPC MSc

Phone

4164806100

Ext

4617

ellen.warner@sunnybrook.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katarzya J Jerzak, MD MSc FRCPC

Organizational Affiliation

University of Toronto

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sunnybrook Odette Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N3M5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Julius, PhD

Phone

4164806100

michael.julius@sunnybrook.ca

First Name & Middle Initial & Last Name & Degree

Ellen Warner, MD FRCPC MSc

First Name & Middle Initial & Last Name & Degree

Arjun Sahgal, MD FRCPC

First Name & Middle Initial & Last Name & Degree

Greg Stanisz, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Learn more about this trial

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

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