| Eligibility |
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
Exclusion Criteria:
- Patients who have not recovered from adverse events of prior therapy to = NCI
CTCAEv4.0 Grade 1.
- Patients receiving any other investigational anti-cancer agents.
- Patients who have received prior treatment with a selective 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 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 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.
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