An Investigational Scan (64Cu-DOTA-Trastuzumab PET/MRI) in Imaging Patients With HER2+ Breast Cancer With Brain Metastasis

Anatomic Stage IV Breast Cancer AJCC v8 Clinical Trial

Official title:

Pilot Study to Evaluate 64Cu-DOTA-Trastuzumab Imaging in Patients With HER2+ Breast Cancer With Brain Metastatsis Treated With Fam-Trastuzumab Deruxtecan

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05376878
• Other study ID #: 21050
• Secondary ID: NCI-2022-0322021
• Status: Recruiting
• Phase: Phase 4
• Start date: December 21, 2022
• Est. completion date: February 25, 2026

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

OUTLINE:

Patients receive trastuzumab intravenously (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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: February 25, 2026
• Est. primary completion date: February 25, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anatomic Stage IV Breast Cancer AJCC v8
• Breast Neoplasms
• Metastatic Breast Carcinoma
• Metastatic Malignant Neoplasm in the Brain
• Neoplasms

Intervention

Other:
• Copper Cu 64-DOTA-Trastuzumab
Given IV

Procedure:
• Magnetic Resonance Imaging
Undergo PET/MRI

Device:
• Positron Emission Tomography
Undergo PET/MRI

Biological:
• Trastuzumab
Given IV
• Trastuzumab Deruxtecan
Given IV

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients with quantifiable 64Cu-DOTA-trastuzumab PET uptake	Percentage of patient with quantifiable 64Cu-DOTA-trastuzumab PET imaging (maximum standardized uptake value[SUVmax]) uptake in brain lesions.	Until disease progression or death, up to 5 years.
Primary	Comparison of average min SUVmax values in responders versus non-responders.	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.	Until disease progression or death, up to 5 years.
Secondary	Progression-free Survival	Estimated using the product-limit method of Kaplan and Meier. Progression defined by any of the following: > 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.	From start of treatment until progression or death from any cause, up to 5 years.