A research study of Palbociclib plus Fulvestrant for patients who previously received endocrine treatment and whose breast cancer has spread to other parts of the body
- Conditions
- Patients with endocrine-resistant metastatic or locally relapsed breast cancer not amenable to treatment with a curative intent ER+/HER2-, enrolled in the AURORA studyMedDRA version: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005387-15-IT
- Lead Sponsor
- INTERNATIONAL BREAST CANCER STUDY GROUP
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 120
Histologically confirmed breast adenocarcinoma that is metastatic or locally relapsed disease not amenable to curative therapy.
- 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 (including chemotherapy, tamoxifen, toremifene, or ovarian
suppression) 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
- ER positive and HER2 negative tumor as assessed by the local laboratory
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Measurable or non-measurable but evaluable disease according to RECIST 1.1. Bone only disease is allowed. Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation.
- Written Informed Consent (IC) for screening procedures and trial participation must be signed and dated by the patient and the Investigator prior to screening.
- Written informed consent to participate in the AURORA program of BIG.
- The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
- Life expectancy >3 months.
- Hematologic status:
- Absolute neutrophil count = 1.5 × 109/L (without growth factor support),
- Platelet count = 100 × 109/L (no transfusion allowed within 2 weeks prior to asessment),
- Hemoglobin = 9 g/dL (transfusion permitted)
- Hepatic status:
- Serum total bilirubin = 1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 3 × ULN)
is allowed.
- 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 = 7.5%.
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
- Prior use of fulvestrant or any CDK inhibitor.
- More than one prior line of 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. Patients with a history of CNS metastases or cord compression are eligible if they
have been definitively treated with local therapy (e.g., radiotherapy,) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before enrollment.
- 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 greater or equal to III, 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 (eg, 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, i.e. strong CYP3A inhibitors/inducers and drugs known to cause QT interval prolongation
- 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 randomization.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method