Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.

NCT03671330 | Completed Phase 2 DMC

• 1 other identifier: CLEE011A2206
• Study Type: interventional
• Target: 327
• Locations: 1 country
• Sites: 24

Brief Summary

This is a Phase II randomized, double-blind, placebo-controlled study involving premenopausal and postmenopausal Chinese women plus an open-label single arm of pharmacokinetic cohort of LEE011 in combination with Letrozole in Chinese postmenopausal women with HR+, HER2- negative advanced breast cancer. Three cohorts of patients will be enrolled: PK cohort, premenopausal cohort, and postmenopausal cohort.

Conditions

Breast Cancer

Keywords

HR+; HER2-; breast cancer; ribociclib; Advanced breast cancer; LEE011; pre- and postmenopausal Chinese women; HR positive; HER2-negative; Endocrine therapy

Outcome Measures

Primary Outcomes (1)

• Progressive free survival (PFS) based on local assessment by RECIST 1.1 guideline

  Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

  The primary analysis will be conducted for pre and postmenopausal cohorts separately when approximately 100 PFS events have been observed in pre- and postmenopausal cohorts (approximately 23 months).

Secondary Outcomes (9)

• Pharmacokinetic (PK) parameter: Cmax

  10 months

• PK parameter: Tmax

  10 months

• PK parameter: AUC024h

  10 months

• Overall Survival (OS)

  50 months

• Overall response rate (ORR)

  50 months

Study Arms (2)

Ribociclib

EXPERIMENTAL

Patients in pre- and postmenopausal cohorts will be randomized in the 1:1 ratio to the experimental arm or the control arm. Premenopausal experimental arm: NSAI + Goserelin + Ribociclib; For pre-menopausal only, patient is an adult, female ≥ 18 years old and \< 60 years old at the time of informed consent. It is the investigators choice for NSAI based on patient's past medical history. Postmenopausal experimental arm: Letrozole + Ribociclib PK Cohort: Open-label ribociclib + Letrozole treatment combination. For postmenopausal only, patient is an adult, female ≥ 18 years old at the time of informed consent

Drug: Ribociclib; Drug: NSAI: Letrozole or Anastrazole; Drug: Letrozole

Ribociclib Placebo

PLACEBO COMPARATOR

Patients in pre- and postmenopausal cohorts will be randomized in the 1:1 ratio to the experimental arm or the control arm. Premenopausal control arm: NSAI + Goserelin + Placebo; For pre-menopausal only, patient is an adult, female ≥ 18 years old and \< 60 years old at the time of informed consent. It is the investigators choice for NSAI based on patient's past medical history. Postmenopausal control arm: Letrozole + Placebo For postmenopausal only, patient is an adult, female ≥ 18 years old at the time of informed consent

Drug: Ribociclib Placebo; Drug: Ribociclib; Drug: NSAI: Letrozole or Anastrazole; Drug: Letrozole; Drug: Goserelin

Interventions

Ribociclib Placebo DRUG

Film-coated tablets for oral use (200 mg x 3) form Day 1 of 21 of each 28 day cycle.

Also known as: LEE011 Placebo

Ribociclib Placebo

Ribociclib DRUG

Film-coated tablets for oral use (200 mg x 3) form Day 1 of 21 of each 28 day cycle.

Also known as: LEE011

Ribociclib; Ribociclib Placebo

NSAI: Letrozole or Anastrazole DRUG

Letrozole: Tablets for oral use, 2.5mg daily (all days of every cycle without interruption). Anastrazole: Tablets for oral use, 1mg daily (all days of every cycle without interruption) For Premenopausal cohort, it is the investigators choice for NSAI based on patients past history. For postmenopausal and PK cohorts, all patients will be on Letrozole.

Ribociclib; Ribociclib Placebo

Letrozole DRUG

Letrozole: Tablets for oral use, 2.5mg daily (all days of every cycle without interruption).

Ribociclib; Ribociclib Placebo

Goserelin DRUG

Subcutaneous implant, 3.6mg on Day 1 of each 28 day cycle

Ribociclib Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER) positive and/or progesterone receptor positive breast cancer by local laboratory (based on most recently analyzed biopsy).
• Patient has HER2-negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
• Patient must have either:
• Measurable disease, i.e., at least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation). OR
• If no measurable disease is present, then at least 1 predominantly lytic bone lesion must be present (patients with no measurable disease and only 1 predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).
• Patient has ECOG performance status 0 or 1.
• For premenopausal cohort:
• Patient is an adult, female ≥ 18 years old and \< 60 years old at the time of informed consent and has signed informed consent before any trial related activities are conducted and according to local guidelines.
• Confirmed negative serum pregnancy test before starting study treatment or patient has had a hysterectomy.
• Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer not amenable to curative therapy (e.g.
• surgery and/or radiotherapy).
• Patients who received ≤ 14 days of a NSAI (letrozole or anastrozole) with or without goserelin or goserelin ≤ 28 days for advanced breast cancer prior to randomization are eligible. Patients must continue treatment with the same hormonal agent + goserelin during the study. No treatment interruption is required for these patients prior to randomization.
• Patients who have received up to 1 line of chemotherapy for advanced breast cancer and have been discontinued 28 days before randomization are eligible.
• For postmenopausal cohort:
• Patient is an adult, female ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.

You may not qualify if:

• Patient who has received a prior CDK4/6 inhibitor.
• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
• Patient with CNS metastases.
• Patient who has not had resolution of clinical and laboratory acute toxicities related to prior anti-cancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade ≤1.
• Patient has a known history of Human immunodeficiency Virus (HIV) infection (testing not mandatory).
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
• Patient is currently receiving any of the substances as defined in the protocol that cannot be discontinued 7 days prior to the start of the treatment:
• For premenopausal cohort:
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and for 21 days after stopping study medication.
• Note: Use of oral (estrogen and progesterone), transdermal, injected or implanted hormonal methods of contraception as well as hormonal replacement therapy is not allowed in this study.
• For postmenopausal cohort:
• \- Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer.
• Note: Patients who received neo (adjuvant) therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole, the disease free interval must be greater than 12 months from the completion of treatment until randomization.
• \- Patients who received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization are eligible.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (24)

Novartis Investigative Site

Hefei, Anhui, 230001, China

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100044, China

Location

Novartis Investigative Site

Chongqing, Chongqing Municipality, 404100, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Shijiazhuang, Hebei, 050011, China

Location

Novartis Investigative Site

Harbin, Heilongjiang, 150081, China

Location

Novartis Investigative Site

Changsha, Hunan, 410013, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

Location

Novartis Investigative Site

Suzhou, Jiangsu, 215004, China

Location

Novartis Investigative Site

Nanchang, Jiangxi, 330009, China

Location

Novartis Investigative Site

Changchun, Jilin, 130021, China

Location

Novartis Investigative Site

Shengyang, Liaoning, 110016, China

Location

Novartis Investigative Site

Shengyang, Liaoning, 110042, China

Location

Novartis Investigative Site

Xian, Shanxi, 710061, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Kunming, Yunnan, 650106, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310006, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310016, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Fuzhou, 350001, China

Location

Novartis Investigative Site

Qingdao, 266000, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Novartis Investigative Site

Tianjin, 300480, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Anastrozole; Letrozole; Goserelin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 14, 2018
• Study Start: August 29, 2018
• Primary Completion: April 25, 2022
• Study Completion: May 9, 2025
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (24)