Clinical Trials /

Palbociclib in Molecularly Characterized ER-positive/HER2-negative Metastatic Breast Cancer



This international, multicenter, prospective single arm Phase II biomarker discovery clinical trial with the primary objective of assessing the association of PFS with gene mutations, gene copy number aberrations and gene signatures in post-menopausal women with hormone receptor positive, HER2-negative metastatic or locally relapsed breast cancer whose disease has progressed after prior adjuvant endocrine therapy or one line systemic treatment, i.e., endocrine treatment or chemotherapy, administered for metastatic disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting


Phase 2

Trial Eligibility


<span class="go-doc-concept go-doc-intervention">Palbociclib</span> in Molecularly Characterized ER-positive/<span class="go-doc-concept go-doc-biomarker">HER2</span>-negative Metastatic <span class="go-doc-concept go-doc-disease">Breast Cancer</span>


  • Brief Title: Palbociclib in Molecularly Characterized ER-positive/HER2-negative Metastatic Breast Cancer
  • Official Title: A Phase II Study of Palbociclib Plus Fulvestrant Versus Placebo Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02536742

    ORG ID: IBCSG 53-14 / BIG 14-04

    Trial Conditions

    Metastatic Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib PD-0332991 Experimental
    Placebo Control
    Fulvestrant Faslodex Experimental, Control

    Trial Purpose

    This international, multicenter, randomized, double-blind, placebo-controlled, Phase II
    clinical trial with the primary objective of demonstrating the superiority of palbociclib in
    combination with fulvestrant over placebo plus fulvestrant in prolonging progression free
    survival (PFS) in post-menopausal women with hormone receptor positive, HER2-negative
    metastatic or locally relapsed breast cancer whose disease has progressed after prior
    endocrine therapy (1st or 2nd line).

    Detailed Description

    Based on the efficacy data for palbociclib in both the preclinical and the clinical setting,
    it is hypothesized that the addition of palbociclib to fulvestrant will result in
    prolongation of PFS for women with ER positive, HER2 negative, endocrine pretreated,
    metastatic or locally advanced breast cancer, as compared to the PFS achieved by placebo
    plus fulvestrant.

    The trial is included in the AURORA program conducted by the Breast International Group
    (BIG), an international study aiming to collect and characterize biological samples,
    including metastatic tissue, from patients with advanced breast cancer. Detailed molecular
    information will be available to identify putative biomarkers of response to study regimens.

    The trial will provide an important addition to the current knowledge on predictive
    biomarkers to palbociclib by providing extensive molecular characterization of the
    metastatic disease and of circulating biomarkers that might be better suited for
    retrospective biologic correlative studies.

    Trial Arms

    Name Type Description Interventions
    Experimental Experimental Palbociclib plus Fulvestrant Palbociclib, Fulvestrant
    Control Placebo Comparator Placebo plus Fulvestrant Placebo, Fulvestrant

    Eligibility Criteria

    Inclusion Criteria:

    - 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.

    Exclusion Criteria:

    - 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
    progressive growth.

    - 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

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Trial Keywords



    HER2 negative