Palbociclib and Bicalutamide in Treating Patients with Androgen Receptor Positive Metastatic Breast Cancer

Inclusion Criteria

• Pathologically confirmed invasive cancer of the breast
• Estrogen receptor (ER)/progesterone receptor (PR) status (ER or PR defined as positive if >= 1%; ER/PR is defined as negative if < 1%): * PHASE I: Patients may have ER/PR(+) or negative (-) breast cancer; ER(+) patients must have progression of disease following 1 prior line of endocrine therapy; progression of disease within 6 months of adjuvant endocrine therapy will be considered 1 line of prior endocrine therapy * PHASE II: Patients must have ER/PR(-) breast cancer
• Human epidermal growth factor receptor 2 (HER2) normal (immunohistochemistry [ICH] 0-1; fluorescence in situ hybridization [FISH] < 2.0)
• Non-measurable or measurable, metastatic disease
• Available tissue for AR testing for research purposes
• Androgen receptor expression testing confirms that the patient’s tumor is AR (+); AR is considered positive if >= 1% of cell nuclei are immunoreactive using the Dako antibody (clone androgen receptor antibody [AR441]); receptor testing may be performed on either primary tumor specimen or tissue from a metastatic site; local testing permitted for eligibility but will require confirmation at Memorial Sloan-Kettering Cancer Center (MSKCC)
• There is no limit to the number of prior chemotherapy or endocrine therapy regimens allowed; patients with ER(+) AR(+) breast cancer must have had at least 1 prior line of endocrine therapy to be eligible for the phase I portion of the trial
• At least 2 weeks since last cytotoxic chemotherapy, hormonal therapy, or radiotherapy; toxicities related to prior therapy must either have returned to grade 1, or baseline (excluding alopecia)
• Patient may receive bisphosphonates/denosumab for the palliation of bone metastases
• If patient has a history of brain metastases or leptomeningeal disease, lesions must be stable for at least 3 months (as documented by either head computed tomography [CT] or brain magnetic resonance imaging [MRI])
• Prior treatment with bicalutamide will not be allowed
• At least 3 weeks from major surgery with full recovery
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Postmenopausal; use of luteinizing hormone-releasing hormone (LHRH) agonist permitted
• Patients must not have another, non-breast, active malignancy that requires treatment
• Women of child-bearing potential must agree to use adequate contraception (barrier method of birth control; abstinence); women must not breast feed while on study
• Ability to understand and the willingness to sign a written informed consent document
• Ability to swallow intact palbociclib capsules and bicalutamide tablets
• Absolute neutrophil count >= 1.5 x 10^9/L
• Hemoglobin >= 9.0 g/dL
• White blood cell count (WBC) >= 3.0 x 10^9/L
• Platelets >= 100 x 10^9/L
• Total bilirubin =< 1.5 x upper limit of normal (ULN) except for patients with known Gilbert syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
• Plasma creatinine =< 1.5 x ULN or creatinine clearance > 50 mL/min (calculated by Cockcroft-Gault method)
• Corrected QT (QTc) interval =< 470 msec

Exclusion Criteria

• Patients who have not recovered from adverse events of prior therapy to =< National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 grade 1
• Patients receiving any other investigational anti-cancer agents
• Patients who have received prior treatment with a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
• Patients who have received prior anti-androgen therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib
• Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including human immunodeficiency virus (HIV), active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (specifically, uncontrolled atrial fibrillation or ventricular dysrhythmias except ventricular premature contractions), or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women and women who are breast-feeding
• Patients with a history of long-QT syndrome or documented family history of long-QT syndrome; patients who must remain on drugs that prolong the QT interval
• Palbociclib is a substrate of cytochrome P450, family 3, subfamily A (CYP3A); caution should be exercised when dosing palbociclib concurrently with CYP3A inducers or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; the following medications with strong potential for interaction are not allowed: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, troglitazone