Phase IIIb Study of Ribociclib + ET in Early Breast Cancer
- Conditions
- Early Breast Cancer
- Interventions
- Registration Number
- NCT05827081
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this open-label, multicenter, phase IIIb, single-arm study is to characterize the efficacy and safety of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a close to clinical practice patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, IIB, and a subset of Stage IIA Early Breast Cancer (EBC).
- Detailed Description
The study consists of Screening, Treatment, and Follow-up periods.
* Treatment Period: all participants who complete screening will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily ET for 36 months (approximately 39 cycles) from the date of first dose. The Treatment Period starts when the patient receives their first dose of ribociclib and ends at the time of the 30-day Safety Follow-up. All treated participants should have a Safety Follow-up call conducted 30 days after the last dose of study treatment.
* Follow-up period: participants will be followed from 30 days after study treatment (i.e., ribociclib) completion/discontinuation (i.e. 30-day Safety Follow-up) until death, withdrawal of consent, lost to follow-up, or until 48 months after the last participant has received their first dose of study treatment (i.e. End of Study \[EOS\]), whichever occurs first.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1400
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Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC).
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Participant has HER2-negative breast cancer.
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Participants may have already received any standard neoadjuvant and/or adjuvant ET, including tamoxifen or toremifene at the time of informed consent signature, but enrollment should occur within 36 months of prior ET start date and participants should have at least 3 years remaining of endocrine adjuvant therapy.
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Participant has no contraindication to receive adjuvant ET in the study.
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Participant 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 III, or
- Anatomic Stage Group IIB, or
- A subset of Anatomic Stage Group IIA
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Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
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Participant has adequate bone marrow and organ function.
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ECG values assessed by KardiaMobile-6L device, or standard 12-lead ECG per local investigator where KardiaMobile-6L cannot be used, as:
- QTcF interval at Screening < 450 msec (QT interval using Fridericia's correction).
- Mean resting heart rate 50-99 beats per minute (determined from the ECG).
Key
- Participant with distant metastases of BC beyond regional lymph nodes (Stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
- Participant is concurrently using other antineoplastic 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.
Other inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ribociclib + endocrine therapy Exemestane 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 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used) Ribociclib + endocrine therapy Letrozole 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 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used) Ribociclib + endocrine therapy Ansastrozole 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 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used) Ribociclib + endocrine therapy Goserelin 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 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used) Ribociclib + endocrine therapy Leuprolide 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 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used) Ribociclib + endocrine therapy Ribociclib 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 36 months (approximately 39 cycles). ET consists of: * For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously. * For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used)
- Primary Outcome Measures
Name Time Method Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years At 3 years iBCFS is defined as the time from the date of first dose to the date of the first event of invasive ipsilateral 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.
The iBCFS rate at 3 years will be assessed.
- Secondary Outcome Measures
Name Time Method Incidence and severity of adverse events (AEs) using CTCAE v4.03 Up to approximately 6 years To evaluate Safety of ribociclib + ET
Invasive Disease-Free Survival (iDFS) Up to approximately 6 years iDFS is defined as the time from the date of first dose of study treatment 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.
Distant Disease-Free Survival (DDFS) Up to approximately 6 years Distant Disease-Free Survival (DDFS) is defined as the time from the date of first dose of study treatment to the date of the first event of recurrence at a distant site, death (any cause), or second primary non-breast invasive cancer (excluding in situ/non-invasive cancers and basal and squamous cell carcinomas of the skin).
DDFS will be assessed using STEEP 2.0 as assessed by the investigator.Distant Relapse-Free Survival (DRFS) Up to approximately 6 years Distant Relapse Free Survival (DRFS) is defined as the time from the date of first dose of study treatment to the date of the first event of recurrence at a distant site or death (any cause). DRFS will be assessed using STEEP 2.0 as assessed by the investigator.
Recurrence-Free Interval (RFI) Up to approximately 6 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.
Relative dose intensity (RDI) of ribociclib Up to 3 years RDI is defined as the ratio of the dose intensity delivered to the planned dose intensity.
Overall Survival (OS) Up to approximately 6 years OS is defined as time from the start of study treatment to date of death due to any cause.
Time To Discontinuation (TTD) of ribociclib Up to 3 years TTD is defined as the time from starting ribociclib to the time to treatment discontinuation due to any cause.
Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score Up to approximately 6 years 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.
Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score Up to approximately 6 years The FACT-ES is a questionnaire that consists of 19 items which assesses endocrine complaints and adverse events.
Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score Up to approximately 6 years The FACIT-F is a 13-item questionnaire designed to assess self-reported fatigue and its impact on daily activities and functions.
Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score Up to approximately 6 years 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.
Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score Up to approximately 6 years 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.
Trial Locations
- Locations (10)
Ocala Research Institute, Inc
🇺🇸Ocala, Florida, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Summit Cancer Care PC
🇺🇸Savannah, Georgia, United States
Hope And Healing Care
🇺🇸Hinsdale, Illinois, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Jackson Oncology Associates
🇺🇸Jackson, Mississippi, United States
Clinical Research Alliance
🇺🇸Lake Success, New York, United States
Novartis Investigative Site
🇰🇷Seoul, Korea, Republic of