- Female gender
- Age 18 years
- Postmenopausal, defined as women with:
- Prior bilateral surgical oophorectomy; or
- Amenorrhea and age 60 years; or
- Age < 60 years and amenorrhea for 12 or more consecutive months in the absence
of alternative pathological or physiological cause and FSH and serum estradiol
levels within the laboratory's reference ranges for postmenopausal women.
- Endocrine resistant disease, defined as one of:
- Relapse while on adjuvant endocrine therapy;
- Relapse within 12 months after completion of adjuvant endocrine therapy;
- Progression of disease under first line endocrine therapy for metastatic and/or
loco-regionally advanced breast cancer.
- Successful enrollment in the AURORA program of BIG.
- ER positive tumor, as assessed by AURORA central laboratory.
- HER2-negative tumor, as assessed by AURORA central laboratory.
- ECOG Performance Status 0-1.
- Measurable or non-measurable but evaluable disease according to RECIST 1.1.
- Written Informed Consent (IC) for screening procedures.
- The patient has been informed of and agrees to data transfer and handling, in
accordance with national data protection guidelines.
- Life expectancy >3 months.
- Hematological status:
- Absolute neutrophil count 1.5 109/L
- Platelet count 100 109/L
- Hemoglobin 9 g/dL
- Hepatic status:
- Serum total bilirubin 1.5 upper limit of normal (ULN).
- AST and ALT 2.5 ULN; if the patient has liver metastases, ALT and AST must
be 5 ULN.
- Glucose in normal range, or well-controlled diabetes defined as an HbA1c level
- Renal status:
- Creatinine 1.5 ULN or creatinine clearance > 60 ml/min.
- International Normalized Ratio (INR) or Prothrombin Time (PT) 1.5 ULN unless
patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
range of intended use of anticoagulant.
- Ability to swallow oral medication.
- Prior use of fulvestrant or any CDK inhibitor.
- Prior chemotherapy for metastatic or locally relapsed disease.
- Previous or current non-breast malignancies within the last 5 years, with the
exception of in situ carcinoma of the cervix, and adequately treated basal cell or
squamous cell carcinoma of the skin.
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis or
leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable
angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade 2, atrial
fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic
congestive heart failure (NYHA functional classification 3), cerebrovascular
accident including transient ischemic attack, or symptomatic pulmonary embolism.
- QTc exceeding 480msec, family or personal history of long or short QT syndrome,
Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
- Uncontrolled electrolyte disorders that can reinforce the QT-prolonging effect of the
drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia).
- Known history of HIV seropositivity. HIV screening is not required at baseline.
- Uncontrolled diabetes defined as HbA1c level > 7.5%.
- Concurrent disease or familial, sociological or geographical condition that would
make the patient inappropriate for trial participation or any serious medical
disorder that would interfere with the patient's safety.
- Dementia, altered mental status, or any psychiatric condition that would prevent the
understanding or rendering of Informed Consent.
- Known abnormalities in coagulation such as bleeding diathesis, or treatment with
anticoagulants precluding intramuscular injections of fulvestrant.
- Treatment with an investigational agent in the 4 weeks before randomization.
- Concurrent treatment with any of the drugs not permitted
- Adverse events (except alopecia) from previous systemic cancer therapy, radiotherapy
or surgery have not recovered to CTCAE v4.0 grade 1 or resolved prior to
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female