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Phase IIIb Study of Ribociclib + ET in Early Breast Cancer (ADJUVANT WIDER)

Primary Purpose

Early Breast Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ribociclib
Letrozole
Ansastrozole
Goserelin
Leuprolide
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Early Breast Cancer focused on measuring HR+, HER2-, EBC, Early breast cancer, Premenopausal, Postmenopausal, Male breast cancer, Ribociclib, LEE011, NSAI, ET, Endocrine therapy, Goserelin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Ribociclib + endocrine therapy

    Arm Description

    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

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    Relative dose intensity (RDI) of ribociclib
    RDI is defined as the ratio of the dose intensity and the planned dose intensity.
    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    April 12, 2023
    Last Updated
    October 16, 2023
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05827081
    Brief Title
    Phase IIIb Study of Ribociclib + ET in Early Breast Cancer
    Acronym
    ADJUVANT WIDER
    Official Title
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 16, 2024 (Anticipated)
    Primary Completion Date
    July 28, 2028 (Anticipated)
    Study Completion Date
    July 29, 2030 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Early Breast Cancer
    Keywords
    HR+, HER2-, EBC, Early breast cancer, Premenopausal, Postmenopausal, Male breast cancer, Ribociclib, LEE011, NSAI, ET, Endocrine therapy, Goserelin

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    2500 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Ribociclib + endocrine therapy
    Arm Type
    Experimental
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Ribociclib
    Intervention Description
    400 mg daily on days 1-21 of a 28 day cycle followed by 7 days rest
    Intervention Type
    Drug
    Intervention Name(s)
    Letrozole
    Intervention Description
    Letrozole 2.5 mg orally once daily continuously
    Intervention Type
    Drug
    Intervention Name(s)
    Ansastrozole
    Intervention Description
    Anastrozole 1 mg orally once daily continuously.
    Intervention Type
    Drug
    Intervention Name(s)
    Goserelin
    Intervention Description
    Goserelin 3.6 mg subcutaneously once every 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Leuprolide
    Intervention Description
    Leuprolide 3.75 mg subcutaneously once every 4 weeks
    Primary Outcome Measure Information:
    Title
    Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years
    Description
    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.
    Time Frame
    At 3 years
    Secondary Outcome Measure Information:
    Title
    Invasive Disease-Free Survival (iDFS) rate at 1, 2, 3, 4 and 5 years
    Description
    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.
    Time Frame
    at years: 1, 2, 3, 4 and 5
    Title
    Recurrence-free interval (RFI) rate at 1, 2 and 3 years
    Description
    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.
    Time Frame
    at years: 1, 2 and 3
    Title
    Relative dose intensity (RDI) of ribociclib
    Description
    RDI is defined as the ratio of the dose intensity and the planned dose intensity.
    Time Frame
    Up to 3 years
    Title
    Overall Survival (OS) rate at 5 years
    Description
    OS is defined as time from the start of study treatment to date of death due to any cause.
    Time Frame
    At 5 years
    Title
    Time To Discontinuation (TTD) of ribociclib
    Description
    TTD is defined as the time from starting treatment to the time to treatment discontinuation due to any cause.
    Time Frame
    Up to 3 years
    Title
    Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score
    Description
    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.
    Time Frame
    Up to 5 years
    Title
    Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score
    Description
    The FACT-ES is a questionnaire that consists of 19 items which assesses endocrine complaints and adverse events.
    Time Frame
    Up to 5 years
    Title
    Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score
    Description
    The FACIT-F is a 13-item questionnaire designed to assess self-reported fatigue and its impact on daily activities and functions.
    Time Frame
    Up to 5 years
    Title
    Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score
    Description
    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.
    Time Frame
    Up to 5 years
    Title
    Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score
    Description
    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.
    Time Frame
    Up to 5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    1-888-669-6682
    Email
    novartis.email@novartis.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    +41613241111
    Email
    novartis.email@novartis.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Novartis Pharmaceuticals
    Organizational Affiliation
    Novartis Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    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 www.clinicalstudydatarequest.com

    Learn more about this trial

    Phase IIIb Study of Ribociclib + ET in Early Breast Cancer

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