Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer

PRIMARY OBJECTIVES:

I. Correlate uptake of 64Cu-DOTA-trastuzumab (copper Cu 64-DOTA-trastuzumab) PET by individual tumors with subsequent tumor response to ado-trastuzumab emtansine as assessed by serial 18F-fludeoxyglucose (FDG) (fludeoxyglucose F 18)/PET-computed tomography (CT).

II. Compare tumor uptake of 64Cu-DOTA-trastuzumab PET between patients who do and patients who do not respond to ado-trastuzumab emtansine.

III. Obtain tumor tissue for subsequent assessment of the presence of putative molecular mechanisms of resistance (MMRs) to ado-trastuzumab emtansine. When funding becomes available, those samples will be used to explore the correlation between the presence of MMRs as assessed by histopathology and tumor response to ado-trastuzumab emtansine both in univariate analysis and in combination with tumor uptake of 64Cu-DOTA-trastuzumab as measured with PET/CT.

OUTLINE:

Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab intravenously (IV) over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks for 1 year after initiation of treatment until disease progression.

After completion of study treatment, patients are followed up for 1 year.

Inclusion criteria

• Participants must be women who have histological confirmation of metastatic invasive breast cancer that has metastasized outside the region of the primary tumor and axilla; biopsy must be obtained prior to initiation of chemotherapy; it should be performed within 28 days prior to enrollment (patients with a biopsy of recurrent disease that is HER2-positive and have not received HER2-directed therapy since the biopsy can exceed the 28-day window up to 6 months); patients must have metastatic disease in lung, liver, soft-tissue or bone to qualify for the study (more than one site is permissible)
• At least 1 site of metastasis >= 20 mm in mean diameter must be identified
• The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)
• Patients may not have received trastuzumab within 6 weeks of projected 64Cu-DOTA-trastuzumab/PET-CT
• Participants must have normal cardiac ejection fraction
• Ability to provide informed consent
• Patients that may need dose reduction to commence cycle 1 treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Negative serum pregnancy test (female of childbearing potential only)
• Patients must have adequate cardiac function; left ventricular ejection fraction (LVEF) >= 50% as determined by multi gated acquisition (MUGA) scan or echocardiogram

Exclusion criteria

• Participants who have received trastuzumab within the prior 36 days
• Participants who are not considered candidates for ado-trastuzumab-emtansine
• No metastatic sites >= 20 mm
• Concurrent malignancy other than skin cancer - Inability to provide informed consent