Palbociclib in Combination With Bicalutamide for the Treatment of AR(+) Metastatic Breast Cancer (MBC)

Inclusion Criteria

• •A patient will be eligible for androgen receptor expression testing (STEP 1) if the following criteria are met:
• •Female
• •Pathologically confirmed invasive cancer of the breast
• •ER/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(-) breast cancer.
• •HER2 normal (IHC 0-1; FISH \< 2.0)
• •Non-measurable or measurable, metastatic disease
• •Available tissue for AR testing for research purposes
• •A patient will be eligible for participation in the therapeutic trial (STEP 2) if the following criteria are met:
• •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 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 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 CT or brain MRI)
• •Prior treatment with bicalutamide will not be allowed
• •At least 3 weeks from major surgery with full recovery
• •ECOG performance status 0-2
• •Age 18 years or greater
• •Postmenopausal. Use of LHRH agonist permitted.
• •Patients must not have another, non-breast, active malignancy that requires treatment.
• •The effects of palbociclib on the developing human fetus at the recommended therapeutic dose are unknown. 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.
• •Adequate organ and marrow function as defined below (ULN indicates institutional upper limit of normal):
• •* Absolute neutrophil count ≥ 1.5 10\^9/
• •* Hemoglobin ≥ 9.0 g/dL
• •* WBC ≥ 3.0 10\^9/L
• •* Platelets ≥ 100 10\^9/L
• •* Total bilirubin ≤ 1.5 ULN except for patients with known Gilbert syndrome
• •* AST(SGOT)/ALT(SGPT) ≤ 3 institutional ULN
• •* Plasma creatinine ≤ 1.5 ULN or Creatinine Clearance \> 50 mL/min (calculated by Cockcroft-Gault method)
• •* QTc interval ≤ 470 msec