First-Line Ribociclib Plus Endocrine Therapy Versus Chemotherapy With or Without Subsequent Endocrine Therapy in Patients With Rapidly Progressive HR-Positive/HER2-Negative Advanced Breast Cancer

August 3, 2026 updated by: The First Affiliated Hospital with Nanjing Medical University

Efficacy and Safety of First-Line Ribociclib Plus Endocrine Therapy Versus Chemotherapy With or Without Subsequent Endocrine Therapy in Patients With Rapidly Progressive HR-Positive/HER2-Negative Advanced Breast Cancer: A Multicenter, Nonrandomized Phase II Study With an External Control

This phase II study focuses on women with rapidly progressive hormone receptor-positive and HER2-negative advanced breast cancer, including patients with symptomatic visceral metastases, rapidly increasing tumor burden, impending organ dysfunction, or highly symptomatic non-visceral disease. These patients often require prompt and effective systemic treatment.

The purpose of the study is to determine whether first-line ribociclib combined with endocrine therapy can provide effective and rapid tumor control compared with chemotherapy-based treatment. Women in the prospective study group receive ribociclib plus endocrine therapy, with ovarian function suppression when clinically indicated. Their outcomes are compared with data from patients previously treated at the same participating hospitals with combination chemotherapy, with or without subsequent endocrine maintenance therapy.

The main outcome is the objective response rate, defined as the proportion of patients whose tumors shrink or disappear. Other outcomes include progression-free survival, overall survival, clinical benefit, time to response, treatment safety, and quality of life.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study focuses on patients with rapidly progressive hormone receptor-positive, HER2-negative advanced breast cancer, a population for whom prompt systemic disease control is clinically important. Rapid progression may include symptomatic visceral metastases, rapidly increasing tumor burden, impending organ dysfunction, or highly symptomatic non-visceral disease.

The study was initially designed as a prospective, multicenter, randomized phase II trial. Owing to difficulties in prospectively recruiting patients to the chemotherapy control arm, the protocol was amended to include a prospective ribociclib plus endocrine therapy cohort and a retrospective external control cohort. Following statistical consultation, objective response rate was designated as the primary endpoint, with progression-free survival retained as a key secondary endpoint.

Under the amended design, eligible patients receiving first-line ribociclib plus endocrine therapy are enrolled prospectively. Their outcomes are compared with an external control cohort selected from patients treated at the same participating hospitals who received first-line combination chemotherapy, with or without subsequent endocrine maintenance therapy. External control patients are identified from electronic medical records and institutional clinical databases and are required to meet eligibility criteria comparable to those applied to the prospective cohort. The historical control period extends from January 2020 to January 2024.

Objective response rate was designated as the primary endpoint because it directly evaluates early antitumor activity in this phase II setting and was used as the basis for the revised sample-size calculation. Progression-free survival remains a key secondary endpoint. To reduce confounding associated with the nonrandomized external-control design, the study will use predefined eligibility criteria, standardized outcome definitions, and propensity score-based methods, including inverse probability weighting and propensity score matching, with additional multivariable analyses as appropriate.

The major protocol amendment was incorporated into Protocol Version 4.0, dated 28 December 2025, and was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University on 21 January 2026 under approval number 2023-SR-880.A1.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
74

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Jiangsu Provincial People's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria for the prospective cohort

  1. Female patient aged 18 years or older.
  2. ECOG PS of 0-2.
  3. Histologically or cytologically confirmed recurrent, metastatic, or unresectable locally advanced breast cancer not amenable to curative surgery or radiotherapy.
  4. HR-positive/HER2-negative disease: ER expression in at least 10% of tumor-cell nuclei; HER2 IHC 0 or 1+, or IHC 2+ with negative FISH/ISH. When metastatic-tissue pathology is available, the metastatic result is preferred.
  5. At least one feature of rapid disease progression, as determined by the investigator: symptomatic visceral metastasis; rapidly progressive disease or impending visceral compromise; or markedly symptomatic nonvisceral disease.
  6. No prior systemic anticancer therapy for recurrent or metastatic disease. Prior neoadjuvant or adjuvant therapy is permitted.
  7. At least one measurable lesion according to RECIST 1.1.
  8. Postmenopausal, premenopausal, or perimenopausal status. Premenopausal or perimenopausal patients must agree to receive OFS.
  9. Adequate baseline organ function: hemoglobin at least 90 g/L; white blood cell count at least 3.5 × 10^9/L; absolute neutrophil count at least 1.5 × 10^9/L; platelet count at least 100 × 10^9/L; serum creatinine not above the institutional ULN; and clinically acceptable hepatic function.
  10. Negative pregnancy test for patients of childbearing potential and agreement to use effective contraception according to applicable product information and institutional requirements.
  11. Written informed consent and ability to comply with treatment and follow-up procedures.

Exclusion criteria for the prospective cohort

  1. Prior systemic anticancer therapy for recurrent or metastatic disease.
  2. Prior CDK4/6 inhibitor therapy in the neoadjuvant or adjuvant setting.
  3. Symptomatic central nervous system metastasis requiring urgent local intervention. Treated, clinically stable, asymptomatic CNS metastasis may be permitted at investigator discretion.
  4. Known contraindication or serious hypersensitivity to ribociclib or the selected endocrine agent.
  5. Clinically significant uncontrolled cardiac disease, arrhythmia, congenital long-QT syndrome, uncorrected electrolyte abnormality, or baseline QTcF at or above 450 ms.
  6. Severe or active cardiovascular, hepatic, respiratory, renal, hematologic, infectious, or psychiatric disease that may increase risk or interfere with efficacy assessment.
  7. Inability to swallow oral medication or clinically significant gastrointestinal disease that may impair drug absorption.
  8. Pregnancy or breastfeeding.
  9. Clinical condition judged by the investigator to preclude safe systemic treatment.
  10. Any other condition that, in the investigator's opinion, makes participation inappropriate.

Eligibility for the historical external control cohort

The external control cohort must satisfy the same core disease, treatment-line, biomarker, rapid-progression, and measurable-disease criteria as the prospective cohort. The following retrospective adaptations are permitted:

  • ECOG PS may be taken from an explicit medical-record entry. If functional descriptions are mapped to ECOG PS according to a prespecified rule, the inferred status will be flagged and excluded in sensitivity analyses.
  • Rapid disease progression will be determined from contemporaneous symptoms, laboratory findings, imaging descriptions, physician notes, and the treatment-decision context.
  • Baseline laboratory values will be the closest available results within the prespecified window before the index chemotherapy date.
  • At least one measurable lesion must be retrospectively assessable according to RECIST 1.1. Patients with unavailable or inadequate imaging will be excluded.
  • Patients with critically missing baseline covariates, treatment details, tumor-response information, or follow-up outcomes will be excluded according to prespecified data-quality rules.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ribociclib combined with ET±OFS
Drug: Ribociclib
Ribociclib is administered orally at a dose of 600 mg once daily on Days 1-21 of each 28-day treatment cycle. It is given in combination with investigator-selected endocrine therapy, including anastrozole, letrozole, exemestane, or fulvestrant. Premenopausal or perimenopausal patients also receive ovarian function suppression with goserelin when indicated. Treatment continues until disease progression, unacceptable toxicity, death, withdrawal of consent, or another protocol-defined reason for discontinuation. Dose interruption or reduction is permitted according to protocol-specified toxicity management criteria.
Other Names:
  • Exemestane
  • Letrozole
  • Anastrozole
  • Goserelin
  • Fulvestrant

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall response rate (ORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression-free survival is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression Free Survival2
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Refers to the time from randomization to disease progression or death after a patient enters a clinical trial and receives second-line therapy.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Time to treatment failure
Time Frame: From randomization to treatment failure or withdrawal from the trial; reasons for withdrawal can be patient request, disease progression, death, or adverse events, whichever came first, assessed up to 100 months
Time to treatment failure is defined as the time from the date of randomization/start of treatment to the earliest of date of progression, date of death due to any cause, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'.
From randomization to treatment failure or withdrawal from the trial; reasons for withdrawal can be patient request, disease progression, death, or adverse events, whichever came first, assessed up to 100 months
Overall survival(OS)
Time Frame: From date of randomization until the date of death from any cause, assessed up to 100 months
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
From date of randomization until the date of death from any cause, assessed up to 100 months
Time To Response (TTR)
Time Frame: From the date of randomization to the first documented response of either CR or PR, whichever came first, assessed up to 100 months
Time to response is defined as the time from the date of randomization to the first documented response of either CR or PR, which must be subsequently confirmed, as defined by RECIST 1.1.
From the date of randomization to the first documented response of either CR or PR, whichever came first, assessed up to 100 months
Clinical benefit rate(CBR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Clinical benefit rate is defined as the proportion of patients with a best overall response of CR, or PR or stable disease, lasting for a duration of at least 24 weeks, as defined by RECIST 1.1.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Functional Assessment of Cancer Therapy - Breast (FACT-B) will be collected to assess health-related QoL, health status, functioning, disease symptoms, side effects, and cancer-related pain.

Descriptive statistics will be used to summarize the overall score at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized.

The distribution of time to definitive 10% deterioration in the global health status from FACT-B questionnaire will be assessed in the two treatment arms. Scores range from 0 to 4. no subscale. 0 score is the worst for social/family and functional wellbeing and 4 is the worst for physical, emotional wellbeing and additional concerns.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Frequency/severity of adverse events, lab abnormalities
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Safety of ribociclib in combination with NSAI and OFS, and combination chemotherapies
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The First Affiliated Hospital with Nanjing Medical University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Affiliated Hospital of Jiangnan University
Jiangyin People's Hospital
Yidu Central Hospital of Weifang
Fuyang Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 9, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 28, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 19, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HERO-KC23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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