Pilot Study to Evaluate 64Cu-DOTA-Trastuzumab Imaging in Patients With HER2+ Breast Cancer With Brain Metastatsis Treated With Fam-Trastuzumab Deruxtecan
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Percent of patients with quantifiable 64Cu-DOTA-trastuzumab PET uptake
Study Overview
Brief Summary
This clinical trial examines an investigational scan (64Cu-DOTA-trastuzumab positron emission tomography [PET]/magnetic resonance imaging [MRI]) in imaging patients with HER2+ breast cancer that has spread to the brain (brain metastasis). Diagnostic procedures, such as 64Cu-DOTA-trastuzumab PET/MRI, may help find HER2+ breast cancer that has spread to the brain and determine whether cancer in the brain takes up trastuzumab, which may predict for response to trastuzumab deruxtecan (the standard of care chemotherapy).
Detailed Description
PRIMARY OBJECTIVES:
I. Evaluate the feasibility of 64Cu-DOTA-trastuzumab PET imaging in patients with HER2+ breast cancer metastatic to the brain.
II. Evaluate if HER2+ breast cancer patients with brain metastasis who are responders to fam-trastuzumab deruxtecan have higher maximum standardized uptake value (SUVmax) (minimum over all lesions in the brain) than non-responders.
SECONDARY OBJECTIVE:
I. Evaluate if the minimum SUVmax of all quantifiable lesions in a given patient is associated with time to progression in the brain.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Documented informed consent of the participant and/or legally authorized representative
- •Women with documented metastatic HER2 positive breast cancer (American Society of Clinical Oncology [ASCO] College of American Pathologist [CAP] guidelines) who have brain metastases
- •Age > 18 years
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •Patients with leptomeningeal disease will be considered eligible
- •Planned therapy with fam-trastuzumab deruxtecan
- •Left ventricular ejection fraction (LVEF) > 50%
- •Absolute neutrophil count (ANC) > 1.5 x 10^9/L
- •Platelets > 100 x 10^9/L
- •Hemoglobin > 9 g/dL
- •Total (T.) bilirubin < 3 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN
- •Creatinine clearance > 30 ml/min (by Cockcroft-Gault formula)
- •Activated partial thromboplastin time (aPTT) < 1.5 x ULN
- •Prior therapy for central nervous system (CNS) disease is allowed, but at least 1 lesion > 1.5 cm is evident on MRI
Exclusion Criteria
- •Need for immediate local intervention for brain metastases
- •Noninfectious interstitial lung disease or pneumonitis requiring glucocorticoids
- •Clinically significant corneal disease
- •Myocardial infarction < 6 months before, congestive heart failure (CHF), unstable angina, or serious cardiac arrhythmia
Arms & Interventions
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)
Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Trastuzumab (Biological)
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)
Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Trastuzumab Deruxtecan (Biological)
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)
Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Copper Cu 64-DOTA-Trastuzumab (Other)
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)
Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Magnetic Resonance Imaging (Procedure)
Treatment ( 64Cu-DOTA-trastuzumab PET/MRI)
Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Positron Emission Tomography (Device)
Outcomes
Primary Outcomes
Percent of patients with quantifiable 64Cu-DOTA-trastuzumab PET uptake
Time Frame: Until disease progression or death, up to 5 years.
Percentage of patient with quantifiable 64Cu-DOTA-trastuzumab PET imaging (maximum standardized uptake value\[SUVmax\]) uptake in brain lesions.
Comparison of average min SUVmax values in responders versus non-responders.
Time Frame: Until disease progression or death, up to 5 years.
Comparison evaluated using a non-parametric test. The lowest SUVmax (minimum SUVmax) across the lesions will be the primary metric used. Response assessment for CNS disease is determined by MRI of the brain using Response Assessment in Neuro-Oncology (RANO) criteria.
Secondary Outcomes
- Progression-free Survival(From start of treatment until progression or death from any cause, up to 5 years.)