Clinical Trials /

Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- Intermediate Risk Early Breast Cancer

NCT03081234

Description:

This is an international, multi-center, randomized, double-blinded, placebo-controlled clinical study evaluating the efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, intermediate risk breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- Intermediate Risk Early Breast Cancer
  • Official Title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, Intermediate Risk Early Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CLEE011H2301
  • NCT ID: NCT03081234

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
RibociclibLEE011Ribociclib + adjuvant endocrine therapy
PlaceboPlacebo + adjuvant endocrine therapy
Adjuvant endocrine therapyRibociclib + adjuvant endocrine therapy

Purpose

This is an international, multi-center, randomized, double-blinded, placebo-controlled clinical study evaluating the efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, intermediate risk breast cancer.

Detailed Description

      While adjuvant endocrine therapy (ET) is effective in reducing risk of recurrence in patients
      with hormone receptor (HR)-positive early breast cancer (EBC), recurrences are still common,
      especially in patients with unfavorable clinical, pathological and/or molecular features.
      Ribociclib, a CDK4/6 inhibitor, demonstrated clinical efficacy with tolerable toxicity when
      added to ET in patients with HR-positive, HER2-negative advanced breast cancer. The purpose
      of this study is to evaluate the effect of addition of ribociclib to standard adjuvant ET on
      invasive disease-free survival in patients with HR+, HER2- intermediate-risk EBC.
    

Trial Arms

NameTypeDescriptionInterventions
Ribociclib + adjuvant endocrine therapyExperimentalRibociclib in combination with standard adjuvant endocrine therapy
  • Ribociclib
  • Adjuvant endocrine therapy
Placebo + adjuvant endocrine therapyActive ComparatorPlacebo in combination with standard adjuvant endocrine therapy
  • Placebo
  • Adjuvant endocrine therapy

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 surgical specimen microscopic margins free from tumor and with available archival
             tumor tissue from the surgical specimen

          -  Patient who have AJCC 8th edition Prognostic Stage Group II

          -  Patient has completed adjuvant radiotherapy (if indicated) according to the
             institutional guidelines 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 neoadjuvant therapy (endocrine therapy or chemotherapy) or 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

          -  Patient with inflammatory breast cancer

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Invasive disease-free survival (iDFS) using STEEP criteria
Time Frame:up to 90 months
Safety Issue:
Description:iDFS is defined as the time from the date of randomization to the date of the first event of local invasive breast recurrence, regional invasive recurrence, distant recurrence, death, contralateral invasive breast cancer, or second primary non-breast invasive cancer, and is assessed locally by investigators.

Secondary Outcome Measures

Measure:Recurrence-free survival (RFS) using STEEP criteria
Time Frame:up to 90 months
Safety Issue:
Description:RFS is defined as the time from date of randomization to date of first event of local invasive breast recurrence, regional invasive recurrence, distant recurrence, or death.
Measure:Distant disease-free survival (DDFS) using STEEP criteria
Time Frame:up to 90 months
Safety Issue:
Description:DDFS is defined as the time from date of randomization to date of first event of distant recurrence, death, or second primary non-breast invasive cancer
Measure:Overall survival (OS)
Time Frame:up to 90 months
Safety Issue:
Description:OS is defined as the time from date of randomization to date of death due to any cause.
Measure:Quality of Life (QOL)
Time Frame:Baseline, 90 months
Safety Issue:
Description:Change from baseline in the physical functioning sub-scale score and global health status/QOL scale score as assessed by EORTC QLQ-C30

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Hormone receptor-positive
  • Estrogen and/or progesterone receptor-positive
  • HER2-negative
  • Intermediate risk early breast cancer
  • Adjuvant
  • Ribociclib
  • LEE011
  • CDK4/6 inhibitor
  • Endocrine therapy
  • Phase III
  • breast carcinoma
  • breast cancer

Last Updated

October 2, 2017