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

Status: Active


This phase I / II trial studies the side effects and best dose of palbociclib when given together with bicalutamide and to see how well they work in treating patients with androgen receptor positive breast cancer that has spread to other places in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Androgens can cause the growth of breast cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Giving palbociclib and bicalutamide together may work better in treating androgen receptor positive breast cancer.

Eligibility Criteria

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 0%): * 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

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536
Memorial Sloan Kettering Bergen
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536

New York

Memorial Sloan Kettering Commack
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536
Memorial Sloan Kettering Nassau
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Ayca Gucalp
Phone: 646-888-4536

Trial Objectives and Outline


I. To determine the recommended phase II dose (RP2D) of palbociclib in combination with bicalutamide. (Phase I)

II. To determine the efficacy of palbociclib in combination with bicalutamide in patients with androgen receptor (AR) positive (+) metastatic breast cancer in terms of the proportion of patients progression free at 6 months. (Phase II)


I. Objective response rate (complete response [CR] + partial response [PR]), clinical benefit rate (CBR) (CR+PR+ stable disease [SD] >= 24 weeks), progression-free survival, safety and tolerability.

II. Evaluate progression-free survival (PFS), CBR and the objective response rate in patients with AR staining of 10% or higher.

III. Further characterize the biology of AR (+) breast cancer and explore biomarkers of response to palbociclib.

IV. Perform pharmacokinetic analyses to evaluate potential drug interactions between palbociclib and bicalutamide.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive palbociclib orally (PO) once daily (QD) for 3 weeks. Patients also receive bicalutamide PO QD for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Ayca Gucalp

Trial IDs

Primary ID 15-207
Secondary IDs NCI-2015-02043 ID NCT02605486