Breast Cancer, HER2-Positive Metastatic Breast Cancer
Conditions
Brief summary
SURVEY-CNS is a feasibility study evaluating whether women and men with HER2-positive metastatic breast cancer can be successfully recruited and randomised to a strategy of central nervous system (CNS) magnetic resonance imaging (MRI) surveillance versus standard of care (no routine CNS surveillance). Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Brain metastases can cause significant symptoms, including headache, nausea, seizures, visual disturbance, motor dysfunction, and cognitive or psychological changes. Although new HER2-directed therapies have improved systemic disease control, CNS progression remains common and is associated with reduced quality of life and survival. Currently, routine brain imaging is not recommended in asymptomatic patients. Brain imaging is typically performed only when neurological symptoms develop. Observational data suggest that patients diagnosed with asymptomatic brain metastases may have better outcomes than those diagnosed after symptoms occur. However, it is not known whether a surveillance strategy is feasible or acceptable to patients. All participants in this study will undergo a baseline contrast-enhanced brain MRI. Patients without evidence of CNS metastases on the baseline scan will be randomised (1:1) to either: CNS surveillance with repeat brain MRI at 6 and 12 months, or No routine surveillance imaging (standard of care), with imaging only if clinically indicated. The primary objective is to determine whether more than 30% of eligible patients approached agree to undergo screening and randomisation. The study will approach up to 193 patients and will be considered feasible if 69 patients consent to screening with intent to randomise. Secondary objectives include: Determining the proportion of patients with previously undetected (occult) CNS metastases at baseline; Determining the incidence of occult CNS metastases during surveillance; Recording symptomatic CNS presentations; Describing management of CNS metastases, including surgery or radiotherapy. Participants will be followed for 14 months from baseline.
Detailed description
HER2-positive metastatic breast cancer is associated with a high cumulative incidence of central nervous system metastases. Advances in systemic HER2-targeted therapies have improved extracranial disease control and overall survival; however, CNS progression remains a major cause of morbidity and mortality. Current standard practice does not include routine CNS surveillance imaging in asymptomatic patients. Brain imaging is typically performed only following the onset of neurological symptoms. Observational registry data suggest that detection of asymptomatic brain metastases may be associated with improved survival compared with symptomatic presentation. Whether a structured surveillance approach is feasible and acceptable to patients has not been prospectively evaluated. SURVEY-CNS is a non-CTIMP, randomised, parallel-group feasibility study conducted in Ireland in collaboration with UK centres running a parallel study under the same protocol. All registered participants will undergo a baseline contrast-enhanced MRI of the brain. Participants with radiologically evident CNS metastases at baseline will not proceed to randomisation and will be managed according to standard clinical practice. Participants without CNS metastases will be randomised in a 1:1 ratio to: Surveillance arm: Brain MRI at 6 months and 12 months Standard-of-care arm: No routine surveillance imaging Randomisation will be stratified by: Oestrogen receptor (ER) status (positive vs negative) Line of metastatic therapy (first line vs second or later) Participants will be followed for 14 months from baseline for: Development of radiologically detected CNS metastases Development of symptomatic CNS disease CNS-directed local therapy (surgery, stereotactic radiosurgery, whole brain radiotherapy) Changes in systemic anti-cancer therapy Survival status The primary endpoint is feasibility, defined as the proportion of eligible patients who consent to screening and randomisation. A single-stage A'Hern design will be used. The study will halt when either 69 patients have consented or 193 patients have been approached. Recruitment pathways will be evaluated using a structured screening log and the SEAR (Screened, Eligible, Approached, Randomised) framework to identify barriers to participation and inform planning of a future definitive trial. This study is designed to determine whether a larger efficacy trial of CNS surveillance in HER2-positive metastatic breast cancer is practicable.
Interventions
DIAGNOSTIC_TESTBrain Magnetic Resonance Imaging (MRI) with Contrast
Contrast-enhanced MRI of the brain performed according to local institutional standards. In the surveillance arm, MRI is performed at baseline, 6 months, and 12 months. In the standard-of-care arm, MRI is performed at baseline only, with additional imaging if clinically indicated.
Sponsors
Royal College of Surgeons, Ireland
The Clatterbridge Cancer Centre NHS Foundation Trust
Royal Marsden NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Masking description
This is a diagnostic surveillance feasibility study. Neither participants nor investigators are blinded to allocation.
Intervention model description
Participants without CNS metastases on baseline MRI will be randomized 1:1 to surveillance MRI versus no routine surveillance. All registered participants undergo a baseline contrast-enhanced brain MRI. Participants with no radiologic evidence of CNS metastases are randomized (1:1) to: Surveillance arm: brain MRI at 6 and 12 months Standard-of-care arm: no routine surveillance imaging Randomization is stratified by: Estrogen receptor (ER) status (positive vs negative) Line of therapy (first-line vs second or later) Participants are followed for 14 months from baseline.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Male or female * Histologically or cytologically confirmed HER2-positive breast cancer * Evidence of metastatic breast cancer * Estrogen receptor (ER) positive or negative disease permitted * Presence of visceral metastatic disease * Receiving active HER2-directed systemic therapy * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Estimated life expectancy greater than 6 months * Ability to provide written informed consent * Willing and able to comply with study procedures and follow-up
Exclusion criteria
* Prior history of brain metastases * History or evidence of leptomeningeal carcinomatosis * Symptoms suggestive of brain metastases at screening * Bone-only metastatic disease * Inability to undergo MRI scanning * Known hypersensitivity or contraindication to MRI contrast agents that cannot - be managed per local standard of care * Significant medical condition or laboratory abnormality that, in the opinion of - the investigator, makes participation inappropriate Inability to provide informed consent * Deemed unsuitable for participation by the principal investigator due to clinical, mobility, or social circumstances
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Eligible Patients Consenting to Screening and Randomisation | Through recruitment completion, an average of 24 months. | The proportion of eligible patients approached who provide written informed consent to undergo baseline contrast-enhanced brain MRI with intent to proceed to randomisation (if no CNS metastases are detected). Feasibility will be determined using a single-stage design, with success defined as more than 30% of approached eligible patients consenting to participate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Occult CNS Metastases at Baseline MRI | At baseline (prior to randomisation) | The proportion of registered participants in whom previously undiagnosed (asymptomatic) CNS metastases are detected on the baseline contrast-enhanced brain MRI prior to randomisation. |
| Proportion of Patients With Radiologically Detected CNS Metastases During Surveillance | Up to 12 months after randomisation | Among randomised participants, the proportion who develop previously undiagnosed CNS metastases detected on scheduled surveillance MRI (surveillance arm) or clinically indicated imaging (standard-of-care arm). |
| Proportion of Patients Developing Symptomatic CNS Disease | Up to 14 months after baseline | The proportion of participants who develop neurological symptoms attributable to CNS metastases, including headache, nausea/vomiting, seizure, visual disturbance, motor dysfunction, coordination impairment, cognitive change, or psychological disturbance. |
| Description of Initial Local Treatment for CNS Metastases | Up to 14 months after baseline | Among participants diagnosed with CNS metastases, the proportion receiving surgery, stereotactic radiosurgery (SRS), or whole brain radiotherapy (WBRT) as initial CNS-directed local therapy. |
| Systemic Anti-Cancer Therapy (SACT) Modification Following CNS Diagnosis | Up to 14 months after baseline | The proportion of participants requiring initiation, cessation, or modification of systemic anti-cancer therapy following diagnosis of CNS metastases. |
Countries
Ireland
Contacts
CONTACTCarlo Palmieri, MD, PHD
Outcome results
None listed