Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer

Inclusion Criteria:

- Adult males or females (aged 18 or older) with histologically confirmed, metastatic
human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or
fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer

- Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy
such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as
a line of therapy and patients previously treated with T-DM1 are eligible.

- Have not been treated with gemcitabine in the metastatic setting

- Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria

- Eastern Cooperative Oncology Group (ECOG) performance status 2≤

- Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either
echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)

- Adequate bone marrow function as indicated by the following: absolute neutrophil count
(ANC) >1500/µL; Platelets ≥100,000/µL; Hemoglobin >10 g/dL

- Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN)

- Adequate liver function, as indicated by bilirubin ≤1.5x ULN, aspartic transaminase
(AST) or alanine transaminase (ALT) <2x ULN unless related to metastatic breast cancer
to the liver (in which case AST/ALT < 5x ULN is allowed).

- Signed informed consent

- Adequate birth control in sexually active women of childbearing potential

Exclusion Criteria:

- Active uncontrolled infection or major concurrent illness which in the opinion of the
investigator would render the participant unsafe to proceed with the study

- Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS
disease (documented by brain magnetic resonance imaging [MRI]) off corticosteroids for
at least 1 month potential participants are eligible.

- Women who are pregnant or lactating

- Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)

- Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator
lesion (unless objective disease recurrence or progression within the radiation portal
has been documented since completion of radiation)

- Other concomitant active malignancies

- History of significant cardiac disease, cardiac risk factors or uncontrolled
arrhythmias

- Ejection fraction <50% or below the lower limit of the institutional normal range,
whichever is lower

- Hypersensitivity to any of the study medications

- Untreated psychiatric conditions preventing informed consent