Phase IIIb Study of Ribociclib + ET in Early Breast Cancer

Study Overview
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Brief Summary
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A open-label, multicenter, phase IIIb, single-arm trial is to evaluate the efficacy of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in close to real world patient population with HR-positive, HER2-negative, Anatomic Stage Group III, IIB or a subset of Stage IIA early Breast Cancer (EBC).

Official Title
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A Phase IIIb Study to Characterize the Effectiveness and Safety of ADJUVANT Ribociclib in Broad Real-World patIent Populations in Stage II anD Stage III HR+/HER2- Early Breast canceR (ADJUVANT WIDER)

Conditions
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Early Breast Cancer

Intervention / Treatment
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* Drug: Ribociclib
* Drug: Letrozole
* Drug: Ansastrozole
* Drug: Goserelin
* Drug: Leuprolide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is an adult, male or female ≥ 18 years of age at the time of informed consent signature. Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer Participant has HER2-negative breast cancer Participants may have already received any standard neoadjuvant and/or adjuvant ET, including tamoxifen or toremifene, at the time of informed consent signature, but enrolment should occur within 24 months and the participant has at least 3 years remaining of endocrine adjuvant therapy. Participant is allowed up to 24 months of prior ET with a capping of 1000 participants who have taken prior ET between 12 and 24 months prior to first study treatment (C1D1). Participant should have at least 3 years remaining of planned ET at first treatment dose (C1D1). Patient after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories: anatomic stage group II or III. Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0,1 or 2. Participant has adequate bone marrow and organ function. Exclusion Criteria: Participant with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery. Participant is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET. Participant has any other concurrent severe and/or uncontrolled medical condition Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ribociclib + endocrine therapy<br>Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for up to 39 cycles. ET consists of: For postmenopausal women: letrozole 2.5 mg orally once daily continuously or anastrozole 1 mg orally once daily continuously. For premenopausal women and men: letrozole 2.5 mg orally once daily continuously or anastrozole 1 mg orally once daily continuously, combined with goserelin 3.6 mg subcutaneously once every 4 weeks or leuprolide 3.75 mg subcutaneously once every 4 weeks | Drug: Ribociclib<br>* 400 mg daily on days 1-21 of a 28 day cycle followed by 7 days rest<br>Drug: Letrozole<br>* Letrozole 2.5 mg orally once daily continuously<br>Drug: Ansastrozole<br>* Anastrozole 1 mg orally once daily continuously.<br>Drug: Goserelin<br>* Goserelin 3.6 mg subcutaneously once every 4 weeks<br>Drug: Leuprolide<br>* Leuprolide 3.75 mg subcutaneously once every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years | iBCFS is defined as the time from the date of first dose to the date of the first event of invasive ipsilatoral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death (any cause), or contralateral invasive BC. iBCFS will be assessed using STEEP criteria version 2.0 (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator. | At 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease-Free Survival (iDFS) rate at 1, 2, 3, 4 and 5 years | iDFS is defined as the time from the date of randomization to the date of the first event of invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death (any cause), contralateral invasive BC, or second primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin). iDFS will be assessed using STEEP 2.0 as assessed by the investigator. | at years: 1, 2, 3, 4 and 5 | 
| Recurrence-free interval (RFI) rate at 1, 2 and 3 years | RFI is defined as the time from date of first dose to date of first event of invasive recurrence in the ipsilateral breast or locoregionally, at a distant site, or death from breast cancer. RFI will be assessed using STEEP 2.0 as per investigator assessment. | at years: 1, 2 and 3 | 
| Relative dose intensity (RDI) of ribociclib | RDI is defined as the ratio of the dose intensity and the planned dose intensity. | Up to 3 years | 
| Overall Survival (OS) rate at 5 years | OS is defined as time from the start of study treatment to date of death due to any cause. | At 5 years | 
| Time To Discontinuation (TTD) of ribociclib | TTD is defined as the time from starting treatment to the time to treatment discontinuation due to any cause. | Up to 3 years | 
| Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score | The FACT-B is a questionnaire that consists of 37 items with items from FACT-General (FACT-G) questionnaire (27 items) and from the Breast Cancer Subscale (BCS, 10 items). FACT-B consists of five subscales that address different aspects of the participant's quality of life: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and BCS. | Up to 5 years | 
| Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score | The FACT-ES is a questionnaire that consists of 19 items which assesses endocrine complaints and adverse events. | Up to 5 years | 
| Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score | The FACIT-F is a 13-item questionnaire designed to assess self-reported fatigue and its impact on daily activities and functions. | Up to 5 years | 
| Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score | EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D-5L health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. | Up to 5 years | 
| Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score | WPAI-GH measures the impact of health problems on the participant's productivity, in paid or unpaid activities, in the last 7 days. It is 6-item scale measuring absenteeism, presenteeism, and impairments in unpaid activity. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HR+, HER2-, EBC, Early breast cancer, Premenopausal, Postmenopausal, Male breast cancer, Ribociclib, LEE011, NSAI, ET, Endocrine therapy, Goserelin