OUTLINE: This is a multi-center trial.
- Palbociclib 125 mg will be administered orally once daily on days 1-21 (D1-D21) of each
28-day cycle. Subjects will not take palbociclib on D22-D28.
- Tamoxifen 20 mg will be administered orally once daily for every day of the 28-day
cycle (i.e., continuously).
Palbociclib should be taken with food in combination with tamoxifen. Subjects should take
their dose at approximately the same time each day.
It is encouraged, but not mandatory, that premenopausal subjects will also receive treatment
with goserelin or equivalent (e.g., Lupron) given as an injectable subcutaneous implant on
D1 of every 28 days cycle or every 3 months.
Disease assessments will be performed at the completion of every 2 cycles.
Treatment will continue until disease progression, unacceptable toxicity, subject refusal,
or subject death either from progression of disease, the therapy itself, or from other
causes. Subjects who voluntarily stop the study, have progressive disease, or unacceptable
toxicities will be followed for a total of 24 months after discontinuation of study drug.
To demonstrate adequate organ function, all screening labs should be performed within 14
days prior to registration for protocol therapy:
Hematological (must meet ALL of the following criteria):
- Absolute neutrophil count (ANC) 1.5 10 9/L
- Hemoglobin 9 g/dL
- Platelet count 100 10 9/L
Renal (must meet ONE of the following criteria):
- Serum creatinine 1.5 ULN
- Serum creatinine > 1.5 ULN, estimated glomerular filtration rate (eGFR) 40 mL/min
Hepatic (must meet ALL of the following criteria):
- Aspartate aminotransferase (AST) 2.5 ULN or 5 ULN for subjects with known
- Alanine aminotransferase (ALT) 2.5 ULN or 5 ULN for subjects with known hepatic
- Total serum bilirubin 1.5 ULN
Subjects must meet all of the following applicable inclusion criteria to participate in
- 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.
- Women with locoregional recurrent or metastatic disease, as determined by biopsy of
the metastatic lesion, not amenable to curative therapy.
- Histologically and/or cytologically confirmed diagnosis of ER positive and/or PR
positive (ER >1%, PR >1%), HER2 negative metastatic 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 (FISH, CISH, or SISH) test is required by local
- Metastatic disease evaluable on imaging studies. Subjects may have measurable disease
as per RECIST 1.1 or bone-only disease. Bone-only subjects are eligible if their
disease can be documented/ evaluated by bone scans, CT or MRI. Their disease will be
assessed using MDA criteria.
- 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.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- 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
- 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
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.
Subjects meeting any of the criteria below may not participate in the study:
- Prior treatment with any CDK 4/6 inhibitor.
- Confirmed diagnosis of HER2 positive disease.
- Known uncontrolled or symptomatic CNS metastases. Subjects with known brain
metastasis will only be eligible after their tumors have been treated with definitive
resection and /or radiotherapy and they are neurologically stable for at least 1
month off steroids.
- Subjects with advanced, symptomatic, visceral spread that have life expectancy less
than 4 months.
- Prior (neo)adjuvant treatment with tamoxifen within the 12 months before study entry.
- Prior history of blood clots, pulmonary embolism or deep vein thrombosis.
- Subjects with impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
- Subject has a concurrent malignancy or malignancy within 3 years of randomization,
with the exception of adequately treated basal cell carcinoma, squamous cell skin
carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- Subject has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, contraindicate subject participation in the
- Subject is currently receiving any of the following substances and cannot be
discontinued 7 days prior to the start of the treatment:
- Known strong inducers or inhibitors of CYP3A4/5, including grapefruit,
grapefruit hybrids, pomelos, star-fruit, and Seville oranges.
- Medications that have a narrow therapeutic window and are predominantly
metabolized through CYP3A4/5.
- Known strong inducers or inhibitors of CYP2D6.
- Subject has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects of surgery.
- Known history of human immunodeficiency virus [(HIV) HIV 1/2 antibodies].
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected) (testing not mandatory)
- Any clinically significant infection defined as any acute viral, bacterial, or fungal
infection that requires specific treatment. NOTE: Anti-infective treatment must be
completed 7 days prior to study registration.
- Any other severe, uncontrolled medical condition, including uncontrolled diabetes
mellitus or unstable congestive heart failure
- Known allergy to palbociclib or any of its excipients
- Presence of any non-healing wound, fracture, or ulcer within 28 days prior to study
- Any condition that, in the opinion of the investigator, might jeopardize the safety
of the subject or interfere with protocol compliance.
- Any mental or medical condition that prevents the subject from giving informed
consent or participating in the trial.
- Treatment with any investigational agent within 28 days prior to registration for
protocol therapy and the subject must have recovered from the acute toxic effects of
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female