Palbociclib Isethionate and Ado-Trastuzumab Emtansine in Treating Patients with Recurrent or Metastatic HER2-Positive Breast Cancer

Inclusion Criteria

• All patients must be informed about the study and have signed a current Institutional Review Board (IRB) approved informed consent
• All patients must have recurrent or metastatic HER2-positive breast cancer; diagnosed by biopsy
• All patients must have previously received trastuzumab and a taxane, separately or in combination and have received prior therapy for metastatic disease
• Tumor must be HER2-positive and retinoblastoma (RB)-proficient; RB-proficiency is determined by tumor biopsy demonstrating RB normal and cyclin-dependent kinase inhibitor 2A (p16in4a) low by immunohistochemistry; RB proficiency means that there is an intact RB pathway indicative of responsiveness to PD-0332991; RB staining is scored on an absent (no nuclear staining), weak (nuclear staining less than observed in endothelial cells and stromal cells surrounding the tumor), positive (nuclear staining at or above surrounding tissue) (0, 0.5, 1 respectively); p16ink4a is a routine clinical stain that is scored using absent, weak, positive, strong (0, 1, 2, 3 respectively); tumors will be scored using (p16)/(RB), where a score of less than 3 is required for inclusion; RB loss is expected to occur in less than 15% of cases; RB – proficiency will be done locally as standard of care and made available for central review at later time points in the study
• Patients must have a performance status of =< 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Bilirubin =< 1.5 mg/dl
• Transaminases < 2.5 x upper limit of normal
• Albumin >= 3 mg/dl
• Creatinine =< 1.3 mg/dl
• Adequate cardiac reserve (ejection fraction [EF] >= 50%)
• Absolute neutrophil count (ANC) >= 1,000/mcL
• Platelets >= 100,000/mcL
• Patients must agree to use dual forms of contraception from the time of consent until 6 months after completion of the study
• Patient must be able to swallow capsules and have no surgical or anatomic condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis
• Left ventricular ejection fraction (LVEF) must be within institutional limits of normal as assessed by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) documented within four weeks prior to first dose of study drug; adequate cardiac reserve ejection fraction (EF) >= 50%
• Hemoglobin >= 9 g/dL
• Baseline corrected QT interval (QTc) =< 480 ms
• Patients with measureable or non-measureable disease are eligible

Exclusion Criteria

• Chemotherapy, radiotherapy or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who have not recovered from the adverse events to < grade 2 due to previous agents administered more than 4 weeks prior to study day 1
• Patients less than 4 weeks post major surgery
• Known active central nervous system (CNS) metastases or carcinomatous meningitis; patients with CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable; however, oral corticosteroids for control of CNS symptoms are not allowed on study
• Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs
• Uncontrolled systemic illness, including but not limited to ongoing or active infection
• Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
• Baseline neuropathy > grade 1
• Known positive for human immunodeficiency virus (HIV); baseline HIV screening is not required
• Pregnant or breast-feeding patients
• Patients who are unable or unwilling to abide by the study protocol or to cooperate fully with the investigator or designee
• Patients who have any known history of liver disease, autoimmune hepatitis, sclerosing cholangitis or are found to be carriers (active disease or not) of hepatitis B and hepatitis C
• Patients receiving medications that have the potential to prolong the QT interval
• Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A) isoenzymes should be ineligible