Breast CancerPhase 2NCT03671330
Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.
A Phase 2 study testing Ribociclib, NSAI: Letrozole or Anastrazole and Goserelin in people with Breast Cancer, run by Novartis Pharmaceuticals at 24 sites in China.
Trial summary
This was a randomized, double-blind, placebo-controlled study conducted in Chinese women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, plus an open-label, single-arm pharmacokinetic (PK) subset in postmenopausal Chinese women with HR+, HER2… Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Ribociclib, NSAI: Letrozole or Anastrazole and Goserelin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 327 participants
- Where
- 24 sitesChina
- Study dates
- 29 Aug 2018to 9 May 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
- Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
Who cannot join
- 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
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- 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.
- Other protocol-defined inclusion/exclusion may apply.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
China24 sites
Novartis Investigative Site
Beijing, Beijing Municipality, 100044
Novartis Investigative Site
Beijing, 100036
Novartis Investigative Site
Changchun, Jilin, 130021
Novartis Investigative Site
Changsha, Hunan, 410013
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Chongqing, Chongqing Municipality, 404100
Novartis Investigative Site
Fuzhou, 350001
Novartis Investigative Site
Guangzhou, Guangdong, 510000
Novartis Investigative Site
Hangzhou, Zhejiang, 310006
Novartis Investigative Site
Hangzhou, Zhejiang, 310016
Novartis Investigative Site
Harbin, Heilongjiang, 150081
Novartis Investigative Site
Hefei, Anhui, 230001
Novartis Investigative Site
Kunming, Yunnan, 650106
Novartis Investigative Site
Nanchang, Jiangxi, 330009
Novartis Investigative Site
Nanjing, Jiangsu, 210029
Novartis Investigative Site
Qingdao, 266000
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Shanghai, 200032
Novartis Investigative Site
Shengyang, Liaoning, 110016
Novartis Investigative Site
Shengyang, Liaoning, 110042
Novartis Investigative Site
Shijiazhuang, Hebei, 050011
Novartis Investigative Site
Suzhou, Jiangsu, 215004
Novartis Investigative Site
Tianjin, 300480
Novartis Investigative Site
Xian, Shanxi, 710061
About this study
Official title: Phase II Randomized, Double-blind, Placebo-controlled Study of LEE011(Ribociclib) or Placebo in Combination With Endocrine Therapy for the Treatment of Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer, Including a Subset With Pharmacokinetic Analysis.
This was a randomized, double-blind, placebo-controlled study conducted in Chinese women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, plus an open-label, single-arm pharmacokinetic (PK) subset in postmenopausal Chinese women with HR+, HER2- advanced breast cancer.
Read the detailed description
The study included three cohorts of subjects: a premenopausal cohort and a postmenopausal cohort, both randomized and double-blind, and an open-label, single-arm pharmacokinetic (PK) cohort of postmenopausal women.
The premenopausal cohort assessed the efficacy and safety of treatment with a non-steroidal aromatase inhibitor (NSAI; letrozole or anastrozole) combined with goserelin and ribociclib, compared with NSAI plus goserelin and placebo. The postmenopausal cohort assessed the efficacy and safety of ribociclib plus letrozole versus placebo plus letrozole.
The study consisted of three periods: screening, treatment, and follow-up.
- Screening phase: The study began with a 28-day screening period during which potential participants were evaluated against inclusion and exclusion criteria before initiating treatment on Day 1.
- Treatment phase: Eligible participants in the premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to one of two treatment arms, while participants in the PK cohort were not randomized. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow-up, or study termination. Following a statistically significant progression-free survival (PFS) benefit observed at the primary analysis and implementation of Protocol Amendment 5 (dated 18-Oct-2022), participants and investigators were unblinded. Participants still receiving placebo were offered the option to cross over to ribociclib, at the investigator's discretion and with participant consent.
- Follow-up phase:
- Safety follow-up: All participants were followed for safety for up to 30 days after the last dose of study treatment, except in cases of death, loss to follow-up, or withdrawal of consent.
- Efficacy follow-up: Tumor assessments were performed at baseline and every 8 weeks (±1 week) from randomization for the first 18 months, then every 12 weeks (±1 week) until 36 months, and thereafter as clinically indicated until progression. Participants who discontinued treatment for reasons other than disease progression continued tumor assessments according to the same schedule until progression, death, withdrawal of consent, or loss to follow-up.
- Survival follow-up: Survival status was assessed every 12 weeks (±1 week) for all participants, regardless of treatment discontinuation reason, unless consent was withdrawn.
The end of the study was defined as the earliest occurrence of one of the following: all participants had discontinued or died; a new clinical study offering ribociclib became available and all ongoing participants were eligible for transfer; or participants still benefiting from treatment could continue receiving it through an alternative setting.
- Conditions
- Breast Cancer
- Being tested
- Ribociclib Placebo, Ribociclib, NSAI: Letrozole or Anastrazole, Goserelin
- Keywords
- Hormone receptor positive (HR+), Human epidermal growth factor receptor 2 negative (HER2-), breast cancer (BC), advanced breast cancer, endocrine therapy (ET), ribociclib (LEE011), pre- and postmenopausal Chinese women
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ribociclib PlaceboDrug
Also called LEE011 Placebo
Film-coated tablets for oral use (200 mg x 3) from days 1 to 21 of each 28 day cycle.
RibociclibDrug
Also called LEE011
Film-coated tablets for oral use (200 mg x 3) from days 1 to 21 of each 28 day cycle.
NSAI: Letrozole or AnastrazoleDrug
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.
GoserelinDrug
Subcutaneous implant, 3.6mg on Day 1 of each 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Ribociclib | Experimental | Patients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm.
Premenopausal experimental arm:
Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Ribociclib. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and < 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history.
Postmenopausal experimental arm:
Letrozole + Ribociclib.
Pharmacokinetic (PK) Cohort:
Open-label treatment with Ribociclib + Letrozole combination. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent. Receives: Drug: Ribociclib; Drug: NSAI: Letrozole or Anastrazole; Drug: Goserelin |
| Ribociclib Placebo | Placebo comparator | Patients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm.
Premenopausal control arm:
Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Placebo. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and < 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history.
Postmenopausal control arm:
Letrozole + Placebo. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent. Receives: Drug: Ribociclib Placebo; Drug: NSAI: Letrozole or Anastrazole; Drug: Goserelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pre and Postmenopausal Cohorts: Progressive Free Survival (PFS) Based on Local Assessment by RECIST 1.1 Guideline
Progression-free survival (PFS) was defined as the time from randomization to the first documented disease progression or death from any cause. PFS was assessed by local investigators based on tumor evaluations using RECIST version 1.1 criteria. Patients who had not experienced progression or death by the analysis cut-off date of 25 April 2022 were censored at the date of their last adequate tumor assessment prior to that cut-off.
Measured: After approximately 100 progression-free survival (PFS) events had been observed in each cohort, using data collected up to the analysis cut-off date of 25-Apr-2022, an average of 43 months.
Secondary outcomes (9)
PK Cohort: Maximum Observed Plasma Concentration (Cmax) of Ribociclib and Its Metabolite LEQ803
Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The maximum plasma concentration (Cmax) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.
Measured: Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
PK Cohort: Time to Maximum Observed Plasma Concentration (Tmax) of Ribociclib and Its Metabolite LEQ803
Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The time to reach maximum plasma concentration (Tmax) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.
Measured: Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
PK Cohort: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24h) of Ribociclib and Its Metabolite LEQ803
Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The area under the concentration-time curve from time zero to 24 hours post-dose (AUC₀-₂₄h) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.
Measured: Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
Pre and Postmenopausal Cohorts: Overall Survival (OS)
Overall Survival (OS) was defined as the time from date of first dose to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date).
Measured: Up to approximately 80 months
Pre and Postmenopausal Cohorts: Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) by Investigator assessment as per RECIST 1.1 criteria:
- CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
- PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 80 months
Pre and Postmenopausal Cohorts: Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) was defined as the proportion of patients achieving a complete response (CR) or partial response (PR) per RECIST 1.1 criteria, or stable disease (SD) lasting at least 24 weeks, based on Investigator assessment using RECIST 1.1 criteria:
- CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
- PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for Progressive Disease (PD).
Measured: Up to approximately 80 months
Pre and Postmenopausal Cohorts: Time To Response (TTR)
Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.
Measured: Up to approximately 80 months
Pre and Postmenopausal Cohorts: Duration of Response (DoR)
Duration of Response (DoR) only applies to participants whose Best Overall Response (BOR) was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to any cause. Participants continuing without progression or death were censored at the date of their last adequate tumor assessment.
Measured: Up to approximately 80 months
Pre and Postmenopausal Cohorts: Time to Definitive Deterioration of ECOG Performance Status From Baseline
Time to definitive deterioration in ECOG performance status was defined as the time from the date of randomization to the date when ECOG performance status had definitively deteriorated by at least 1 category compared with baseline. Deterioration was considered definitive if there was no subsequent improvement in ECOG performance status back to the baseline category or above. The ECOG performance status scale assesses a patient's functional level, ranging from 0 (fully active) to 5 (dead). Patients were censored if no definitive deterioration in ECOG performance status was observed before the first to occur between: (i) the analysis cut-off date, and (ii) the date when a new anti-neoplastic therapy was started. The censoring date was the date of the last performance status assessment prior to cut-off/start of new anti-neoplastic therapy. Time to definitive deterioration of ECOG performance status from baseline was estimated by using the Kaplan-Meier method.
Measured: Baseline up to approximately 43 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2018
- Study start29 Aug 2018
- Primary completion25 Apr 2022
- Study completion9 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 327 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03671330
- Sponsor's protocol ID
- CLEE011A2206
- Status last verified
- Jun 2026
- First submitted
- 12 Sep 2018
- Last updated
- 8 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.