A Study of Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Metastatic Breast Cancer

Inclusion Criteria

• Histologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.
• Patients 18 years of age or older, Female patients should be either:
• Postmenopausal, as defined by at least one of the following criteria:
• Age >=60 years;
• Age 2500/mL
• absolute neutrophil count > 1,000/mL
• platelets > 100,000/mL"

Adequate hepatic function:

• total bilirubin within normal institutional limits (unless Gilbert's disease with elevated indirect bilirubin only)
• aspartate aminotransferase (AST) / (serum glutamic-oxaloacetic transaminase (SGOT) 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.

QTc (Bazett) = QT/√RR

• Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, symptomatic congestive heart failure, or cerebrovascular accident excluding transient ischemic attack.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE v4.0 Grade >1.
• Prior hematopoietic stem cell or bone marrow transplantation.
• Abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants (that cannot be safely held for biopsy) that would preclude tumor and skin biopsies.
• For fulvestrant: Ongoing anticoagulation that would preclude an IM injection
• For tamoxifen: Documented hypercoagulable state not receiving anticoagulation
• Known or possible hypersensitivity to palbociclib (CTCAE v4.0).
• Known human immunodeficiency virus infection.
• Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Participation in other studies involving investigational drug(s) (Phases 1-4) within 2 weeks before randomization the current study.
• Women should not become pregnant or breastfeed whilst on this study. Birth control methods are acceptable and will be discussed with study participants.