Clinical Trials /

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

NCT03078751

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer
  • Official Title: An Open Label, Multi-center Protocol for U.S. Patients Enrolled in a Study of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, High Risk Early Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CLEE011G2301
  • SECONDARY ID: 2014-001795-53
  • NCT ID: NCT03078751

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
RibociclibLEE011Ribociclib + adjuvant endocrine therapy (ET)
Adjuvant endocrine therapyPlacebo + adjuvant endocrine therapy (ET)
PlaceboPlacebo + adjuvant endocrine therapy (ET)

Purpose

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

Detailed Description

      The purpose of this study was to evaluate the preliminary safety and tolerability of
      ribociclib to standard adjuvant endocrine therapy (ET) in patients with hormone receptor (HR)
      positive, Human Epidermal Growth Factor Receptor2 (HER2) negative high risk early breast
      cancer (EBC).

      Originally, this was a randomized, Phase III, double-blind, placebo-controlled, multi-center,
      international study to evaluate efficacy and safety of ribociclib with ET as an adjuvant
      treatment in patients with HR-positive, HER2-negative, high risk EBC.

      Patients were randomized at a ratio of 1:1 to receive either ribociclib or placebo for
      approximately 24 months in combination with a standard adjuvant ET with ET continued for at
      least 60 months.

      However, following a review of the ribociclib development program strategy, a decision was
      taken to explore a different approach by initiating a single Phase III study for simplicity
      of trial logistics and for the purpose of analyzing the overall population through a single
      clinical trial. Therefore, this study was closed to enrollment early and was amended to be an
      open label, multi-center Phase II study conducted in the US only. All randomized patients
      were unblinded; patients randomized to placebo were permanently discontinued from the study
      and patients randomized to ribociclib were offered the option to continue treatment with
      ribociclib + ET.

      The study included a screening phase (28 days), a treatment phase composed of maximum of 26
      cycles of ribociclib in combination with ET (approximately 24 months) or until disease
      recurrence, intolerable toxicity, withdrawal of consent, or discontinuation from the study
      treatment for any other reason, whichever was earlier, and a 30 days safety follow up from
      last dose of ribociclib. Ribociclib was given orally once a day on days 1 to 21 in each 28
      days cycle.

      Safety was assessed for each patient until 30 days after the last dose of ribociclib and
      included routine safety monitoring except in case of death, loss to follow up or withdrawal
      of consent.
    

Trial Arms

NameTypeDescriptionInterventions
Ribociclib + adjuvant endocrine therapy (ET)ExperimentalPatients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)
  • Ribociclib
  • Adjuvant endocrine therapy
Placebo + adjuvant endocrine therapy (ET)Placebo ComparatorPatients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
  • Adjuvant endocrine therapy
  • Placebo

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

Primary Outcome Measures

Measure:Number of Participants With Adverse Events and Serious Adverse Events
Time Frame:Up to 26 months
Safety Issue:
Description:These are the number of participants who had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Novartis Pharmaceuticals

Trial 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

Last Updated

March 17, 2021