Adjuvant Ribociclib with Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer (EarLEE-1).

Phase 1

Conditions: Hormone receptor-positive, Estrogen and/or progesterone receptor-positive, HER2-negative, High risk early breast cancer
MedDRA version: 20.0Level: LLTClassification code 10006203Term: Breast cancer stage unspecifiedSystem Organ Class: 100000020819
MedDRA version: 20.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 100000115074
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001795-53-CZ

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2000

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

Other inclusion criteria as per full protocol may apply.
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 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1200

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare invasive disease-free survival (iDFS) for ribociclib + ET versus placebo + ET in patients with HR-positive, HER2-negative, EBC with high risk of recurrence;Secondary Objective: 1. To evaluate the two treatment groups with respect to recurrence-free survival (RFS)<br>2. To evaluate the two treatment groups with respect to distant disease-free survival (DDFS)<br>3. To evaluate the two treatment groups with respect to overall survival (OS)<br>4. To evaluate patients reported outcomes for healthrelated quality of life in the two treatment groups<br>5. To evaluate safety and tolerability of the treatment regimen;Primary end point(s): Invasive disease-free survival (iDFS) using STEEP criteria;Timepoint(s) of evaluation of this end point: up to 54 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Recurrence-free survival (RFS) using STEEP criteria<br>- Distant disease-free survival (DDFS) using STEEP criteria<br>- Overall survival (OS)<br>- Quality of Life (QoL);Timepoint(s) of evaluation of this end point: - up to 77 months<br>- up to 77 months<br>- up to 77 months<br>- Baseline and up to 77 months

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