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

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.

• [18F]-FDG (Drug): \[18F\]-FDG will be injected prior to PET/MRI imaging up to three times over the course of six months.

Primary outcomes

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

Secondary outcomes

• Follow-up [Baseline through 5 year 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).
• Changes in ADC (mm2/sec) from MRI. [Baseline through 2 months]: Compare percent change from imaging visit 2 to the baseline.
• Changes in SER from MRI. [Baseline through 2 months]: Compare percent change from imaging visit 2 to the baseline.
• Changes in SUV from PET. [Baseline through 2 months]: Compare percent change from imaging visit 2 to the baseline.

Sex: Female, ages: 18 Years to 75 Years

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)

• Anna Sorace, PhD, Principal investigator, University of Alabama at Birmingham