Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Ribociclib; Adjuvant endocrine therapy; Placebo
Intervention description: Ribociclib 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months).
Ribociclib was supplied in the form of 200 mg film-coated tablets taken by mouth.; Letrozole 2.5 mg by mouth daily, or anastrozole 1 mg by mouth daily, exemestane 25 mg by mouth daily, tamoxifen 20 mg by mouth daily, for a total duration of at least 60 months. In premenopausal women, a GnRH agonist administered every 28 days.; Placebo 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months).
Placebo was supplied in the form of 200 mg film-coated tablets taken by mouth.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: The trial used to be a placebo-controlled, blinded trial. It was amended to an open-label trial after protocol amendment 2.
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hormone receptor-positive; Estrogen and/or progesterone receptor-positive; HER2-negative; High risk early breast cancer; Adjuvant; Ribociclib; LEE011; CDK4/6 inhibitor; Endocrine therapy; Phase II; Breast carcinoma; Breast cancer

Summary:

      This was an open label, multi-center protocol for U.S. patients enrolled in the study of
      ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone
      receptor-positive, HER2-negative, high risk early breast cancer
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Histologically confirmed unilateral primary invasive adenocarcinoma of the breast

          -  Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast
             cancer

          -  Patient is after surgical resection of the tumor where tumor was removed completely,
             with the final surgical specimen microscopic margins free from tumor and with
             available archival tumor tissue from the surgical specimen

          -  Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage
             Group III tumor; or patient who received neoadjuvant chemotherapy and have 1 or more
             ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in
             lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue

          -  Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles
             or ≥ 12 weeks which included taxanes prior to screening

          -  Patient has completed adjuvant radiotherapy (if indicated) prior to screening

          -  Patient may already have initiated adjuvant endocrine therapy (ET) at the time of
             randomization, but randomization must take place within 52 weeks of date of initial
             histological diagnosis of breast cancer and within 12 weeks of initiating ET

          -  ECOG Performance Status 0 or 1

          -  Adequate bone marrow and organ function

          -  Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within
             normal limits

          -  QTcF interval < 450 msec and mean resting heart rate 50-90 bpm

        Key Exclusion Criteria:

          -  Prior treatment with CDK4/6 inhibitor

          -  Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in
             risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last
             2 years

          -  Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for
             doxorubicin or 900 mg/m² or more for epirubicin

          -  Distant metastases of breast cancer beyond regional lymph nodes

          -  Patient has not recovered from clinical and laboratory acute toxicities of
             chemotherapy, radiotherapy and surgery

          -  Clinically significant, uncontrolled heart disease and/or cardiac repolarization
             abnormality, or clinically significant cardiac arrhythmias

          -  Uncontrolled hypertension with systolic blood pressure >160 mmHg

          -  Patient is currently receiving any of the prohibited substances that cannot be
             discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal
             supplements, and/or fruits and their juices that are known as strong inhibitors or
             inducers of CYP3A4/5; medications that have a narrow therapeutic window and are
             predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior
             to starting study drug, or who have not fully recovered from side effects of such
             treatment; concomitant medications with a known risk to prolong the QT interval and/or
             known to cause torsades de points that cannot be discontinued or replaced by safe
             alternative medication.

          -  Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or
             breast-feed during the study

          -  Women of child-bearing potential unless they are using highly effective methods of
             contraception during the study treatment and for 21 days after stopping the study
             treatment.