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

NCT03081234 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: CLEE011H2301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (1)

• Invasive disease-free survival (iDFS) using STEEP criteria

  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.

  up to 90 months

Secondary Outcomes (4)

• Recurrence-free survival (RFS) using STEEP criteria

  up to 90 months

• Distant disease-free survival (DDFS) using STEEP criteria

  up to 90 months

• Overall survival (OS)

  up to 90 months

• Quality of Life (QOL)

  Baseline, 90 months

Study Arms (2)

Ribociclib + adjuvant endocrine therapy

EXPERIMENTAL

Ribociclib in combination with standard adjuvant endocrine therapy

Drug: Ribociclib; Drug: Adjuvant endocrine therapy

Placebo + adjuvant endocrine therapy

ACTIVE COMPARATOR

Placebo in combination with standard adjuvant endocrine therapy

Drug: Placebo; Drug: Adjuvant endocrine therapy

Interventions

Ribociclib DRUG

Ribociclib 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Ribociclib will be supplied in the form of 200 mg tablets.

Also known as: LEE011

Ribociclib + adjuvant endocrine therapy

Placebo DRUG

Placebo 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Placebo will be supplied in the form of 200 mg tablets.

Placebo + adjuvant endocrine therapy

Adjuvant endocrine therapy DRUG

Tamoxifen 20 mg daily, or letrozole 2.5 mg daily, or anastrozole 1 mg daily, or exemestane 25 mg daily (male patients will be treated with tamoxifen 20 mg daily) for a total duration of at least 60 months. In premenopausal women, adjuvant endocrine therapy may include GnRH agonist administered every 28 days.

Placebo + adjuvant endocrine therapy; Ribociclib + adjuvant endocrine therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Related Publications (2)

• Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007 May 20;25(15):2127-32. doi: 10.1200/JCO.2006.10.3523.

  PMID: 17513820 RESULT

• Hortobagyi GN, Connolly JL, D'Orsi CJ, et al (2017). Breast. From AJCC Cancer Staging Manual 8th ed. By Amin MB, Edge S, Greene FL, et al. Springer

  RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 16, 2017
• Study Start: March 31, 2018
• Primary Completion: November 17, 2025
• Study Completion: November 17, 2025
• Last Updated: March 15, 2018

Record last verified: 2018-03