Monitoring Early Response to Targeted Therapy in Stage IV HER2+ Breast Cancer Patients With Advanced PET/MR Imaging

Monitoring Early Response to Targeted Therapy in Stage IV Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer Patients With Advanced Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)

The purpose of the study is to see if a new group of imaging tests can help identify response to stage IV HER2+ breast cancer before treatment.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: [18F]-FDG

Detailed Description

The purpose of this study is to see if a new group of imaging tests can help identify response to stage IV human epidermal growth factor receptor 2 positive (HER2+) breast cancer before and during treatment. This study will test a new method for monitoring treatment. The investigators will use [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) to look at previously diagnosed stage IV breast cancer and image up to three times during therapy. FDG is a non-natural amino acid with a radioactive tag that is used clinically for staging of disease. However, the role of FDG-PET/MRI for imaging response in breast cancer is not currently clear. PET/MRI is a new imaging technique that combines PET and MRI into a single study.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Anna Sorace, PhD; Phone Number: 205-934-3116; Email: asorace@uabmc.edu
• Study Contact Backup: Name: April Riddle, BSRT; Phone Number: 205-934-6504; Email: ariddle@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • The University of Alabama at Birmingham
      • Contact: April Riddle, BSRT; Phone Number: 205-934-6504; Email: ariddle@uabmc.edu
      • Principal Investigator: Anna Sorace, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be ≥ 18 years old and ≤ 75 years old
• Patients with HER2+ metastatic breast cancer
• HER2-positive breast cancer prospectively determined on the primary tumor by a local pathology laboratory and defined as immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) (defined by ISH ratio of ≥ 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies). Only one positive result is required for eligibility
• Estrogen/progesterone receptor positive OR negative disease allowed
• Patients must have measurable disease in one metastatic lesion per RECIST v 1.1
• Stage IV HER2+ breast cancer patients eligible for a new therapeutic regimen that includes HER2-targeted treatment who are naïve to that regimen
• Estimated life expectancy of greater than six months

Exclusion Criteria:

• Children, less than 18 years of age, will be excluded from this study
• Metastatic breast cancer patients who are HER2 positive and have already started their current HER2-targeted therapy regimen for metastatic disease
• Patients who have not recovered from grade 2 or higher toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment
• Patient is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 7 months after the last dose of study treatment
• Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection that requires systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
• Patients found to have constitutionally present non-magnetic resonance (MR) compatible ferromagnetic materials
• Unable to lie still on the imaging table for one (1) hour
• Inability to receive gadolinium-based contrast agent
• Patients for whom a PET/MRI is technically not feasible (e.g. breast volume, obesity, > body mass index (BMI) 36)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]-Fluorodeoxyglucose (FDG) PET/ MRI	Drug: [18F]-FDG; [18F]-FDG will be injected prior to PET/MRI imaging up to three times over the course of six months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in SER from MRI	Compare percent change of SER from imaging visit 3 to the baseline.	Baseline through 6 months
Changes in ADC from MRI	Compare percent change of ADC (mm2/sec) from imaging visit 3 to the baseline.	Baseline through 6 months
Changes in SUV from PET	Compare percent change of SUV from imaging visit 3 to the baseline.	Baseline through 6 months
Baseline measure of PET standardized uptake value (SUV).	Compare baseline metrics from PET/MRI	Baseline imaging visit 1
Baseline measure of apparent diffusion coefficient (ADC) in mm2/sec from MRI.	Compare baseline metrics from PET/MRI	Baseline imaging visit 1
Baseline measure of signal enhancement ratio (SER) from MRI.	Compare baseline metrics from PET/MRI	Baseline imaging visit 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in ADC (mm2/sec) from MRI.	Compare percent change from imaging visit 2 to the baseline.	Baseline through 2 months
Changes in SER from MRI.	Compare percent change from imaging visit 2 to the baseline.	Baseline through 2 months
Changes in SUV from PET.	Compare percent change from imaging visit 2 to the baseline.	Baseline through 2 months
Follow-up	Compare changes in imaging metrics to disease progression (defined as clinical progression of disease through increase in lesion size or increase in number of lesions).	Baseline through 5 year follow-up

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Anna Sorace, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: MRI; FDG-PET; quantitative imaging
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: R19-149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes