NCT02278120

Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer

A Phase III Randomized, Double-blind, Placebo-controlled Study of LEE011 or Placebo in Combination With Tamoxifen and Goserelin or a Non-steroidal Aromatase Inhibitor (NSAI) and Goserelin for the Treatment of Premenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 672 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: Female
• Age: 18 Years – 59 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to determine whether treatment with tamoxifen or a non-steroidal aromatase inhibitors (NSAI) + goserelin + LEE011 prolonged progression-free survival (PFS) compared to treatment with tamoxifen or a NSAI + goserelin + placebo in premenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.

Detailed description

This was a randomized, Phase III, double-blind, global study comparing the treatment efficacy and safety of ribociclib + goserelin + tamoxifen or a NSAI (letrozole or anastrozole) versus placebo + goserelin + tamoxifen or a NSAI in premenopausal women with HR+, HER2- advanced breast cancer. Eligible participants were randomized in a 1:1 ratio to either the ribociclib arm or the placebo arm. Study treatment continued until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. Participants who discontinued treatment due to reasons other than disease progression or withdrawal of consent for efficacy follow-up continued to be monitored until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy follow-up). All participants who discontinued treatment were followed for survival until the predetermined number of overall survival (OS) events was reached. Following the final OS analysis (performed when approximately 189 deaths were recorded) and with protocol amendment 6 (dated 18-Jul-2019), participants and investigators were unblinded and those participants in the placebo arm had the opportunity to cross-over to the ribociclib arm to receive ribociclib + goserelin + NSAI. Cross-over was optional and was conducted at the investigator's discretion and upon participant consent.

Conditions

• Advanced Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Ribociclib	Ribociclib (600 mg, in three 200 mg hard gelatin capsules) was administered orally once daily on Days 1-21 of each 28-day cycle.
DRUG	Tamoxifen	Tamoxifen (20 mg, tablets) was administered orally on a continuous daily schedule (days 1-28 of each 28-day cycle)
DRUG	Letrozole	Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle)
DRUG	Anastrozole	Anastrozole (1 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle)
DRUG	Goserelin	Goserelin (3.6 mg, subcutaneous implant) was administered on day 1 of every 28-day cycle
DRUG	Placebo	Placebo (hard gelatin capsules) was administered orally once daily on Days 1-21 of each 28-day cycle.

Timeline

• Start date: 2014-11-20
• Primary completion: 2017-08-21
• Completion: 2023-04-20
• First posted: 2014-10-29
• Last updated: 2024-03-12
• Results posted: 2019-02-26

Locations

183 sites across 30 countries: United States, Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Colombia, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Lebanon, Malaysia, Mexico, Poland, Portugal, Russia, Saudi Arabia, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Arab Emirates

Regulatory

• FDA-regulated drug study