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

• Status: Active, not recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to test the safety and effectiveness of the investigational drug, palbociclib with bicalutamide for the treatment of triple negative, androgen receptor positive breast cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: Pfizer
• Treatments: Bicalutamide; Palbociclib

Criteria

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.