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