Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

Male or female ≥ 18 years of age at time of consent. NOTE: Both pre- and post-menopausal women are eligible. Pre-menopausal status is defined as either:

* Last menstrual period within the last 12 months.

* In case of therapy-induced amenorrhea, plasma estradiol and /or FSH is in the premenopausal range per local normal range.

Locally advanced, locoregionally recurrent, or metastatic disease, not amenable to curative therapy. NOTE: Although not required as a protocol procedure, a patient with a new metastatic lesion should be considered for biopsy whenever possible to reassess ER/PR/HER2 status if clinically indicated. If a biopsy is prospectively done as part of standard of care, the study would like to store samples for correlative research.

Histologically and/or cytologically confirmed diagnosis of ER positive and/or PR positive (ER \>1%, PR \>1%), HER2 negative breast cancer. NOTE: Subject has HER2-negative breast cancer (based on most recently analyzed biopsy) is defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (e.g. FISH, CISH, SISH, DISH, etc.) test is required by local laboratory testing.

No prior systemic anti-cancer therapy for advanced HR+ disease. NOTE: Subjects receiving adjuvant treatment with aromatase inhibitors at time of recurrence are allowed to participate. There is no AI washout period required.

Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

Adequate hepatic function within 14 days prior to registration for protocol therapy defined as meeting all of the following criteria:

* aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases and

* alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases and

* total serum bilirubin ≤ 1.5 × ULN

Adequate renal function within 14 days prior to registration for protocol therapy defined by either of the following criteria:

* serum creatinine ≤ 1.5 × ULN

* OR if serum creatinine \> 1.5 × ULN, estimated glomerular filtration rate (eGFR) ≥ 40 mL/min

Adequate hematologic function within 14 days prior to registration for protocol therapy defined as meeting all of the following criteria:

* hemoglobin ≥ 9 g/dL

* and absolute neutrophil count (ANC) ≥ 1.5 × 109/L

* and platelet count ≥ 100 × 109/L

Provided written informed consent and Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization for release of personal health information, approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC). NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required within 72 hours of study registration from women of childbearing potential. If the urine test cannot be confirmed as negative, a serum pregnancy test will be required.

Women of childbearing potential (WOCP) must be willing to use two effective methods of birth control such as use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence for the course of the study until 120 days after the last dose of study drug. The use of hormonal contraceptives is discouraged. NOTE: Women are considered to be of childbearing potential unless they are postmenopausal for at least 12 consecutive months or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Male subjects capable of fathering a child must agree to use adequate contraception or total abstinence for the course of the study until 120 days after the last dose of the study drug.

NOTE: Male subjects will be considered as capable of fathering a child unless they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition).

Co-enrollment in an imaging biomarker study or other non-therapeutic study is allowed.

What this study is about