Phase IIIb Study of Ribociclib + ET in Early Breast Cancer

NCT05827081
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
1,400
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Lead sponsor
Novartis Pharmaceuticals
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Start date
2024-02-28
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Number of sites
228
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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).
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Acronym
Adjuvant WIDER
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Short title
Phase IIIb Study of Ribociclib + ET in Early Breast Cancer
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Official title
A Phase IIIb Study to Characterize the Efficacy and Safety of Adjuvant Ribociclib Plus Endocrine Therapy in a Close-to-clinical Practice Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2030-09-20
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First posted
2023-04-24
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Registry last updated
2026-08-27
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Primary completion date
2029-09-07
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Start date
2024-02-28
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Participants
1,400
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Participant count basis
Estimated
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Planned participants
1,400
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Protocol amendments
5
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Number of sites
228
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Novartis Pharmaceuticals
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05827081
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ClinicalTrials.gov ID
NCT05827081
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Registry record
Open registry record
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Allocation
Not applicable
Model
Single group
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years

    Timeframe: 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.

  1. Incidence and severity of adverse events (AEs) using CTCAE v4.03

    Timeframe: Up to approximately 6 years

    To evaluate Safety of ribociclib + ET

  2. Invasive Disease-Free Survival (iDFS)

    Timeframe: 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.

  3. Distant Disease-Free Survival (DDFS)

    Timeframe: 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.

  4. Distant Relapse-Free Survival (DRFS)

    Timeframe: 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.

  5. Recurrence-Free Interval (RFI)

    Timeframe: 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.

  6. Relative dose intensity (RDI) of ribociclib

    Timeframe: Up to 3 years

    RDI is defined as the ratio of the dose intensity delivered to the planned dose intensity.

  7. Overall Survival (OS)

    Timeframe: Up to approximately 6 years

    OS is defined as time from the start of study treatment to date of death due to any cause.

  8. Time To Discontinuation (TTD) of ribociclib

    Timeframe: Up to 3 years

    TTD is defined as the time from starting ribociclib to the time to treatment discontinuation due to any cause.

  9. Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score

    Timeframe: 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.

  10. Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score

    Timeframe: Up to approximately 6 years

    The FACT-ES is a questionnaire that consists of 19 items which assesses endocrine complaints and adverse events.

  11. Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score

    Timeframe: 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.

  12. Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score

    Timeframe: 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.

  13. Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score

    Timeframe: 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.

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
100 Years
Healthy volunteers
No

Key Inclusion criteria:

  • Participant is an adult, male or female ≥ 18 years of age at the time of informed consent form signature (IC).

  • Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC) based on the most recently analyzed tissue sample tested by a local laboratory prior to enrollment.

  • Participant has HER2- BC 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 based on the most recently analyzed tissue sample.

  • 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.

  • For participants with prior ET treatment > 12 months, restaging is highly recommended (unless contradictory to local regulations) to rule out disease recurrence prior to enrollment.

  • The number of participants with prior ET between 12 and 36 months will be capped at 30%. The cap will not apply to Black or African American participants.

  • Participant has no contraindication to receive adjuvant ET in the study.

  • 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.

  • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.

  • Participant has adequate bone marrow and organ function.

  • 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 Exclusion criteria:

  • 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 that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol, or limit life expectancy to ≤5 years.
  • 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.
  • Women of child-bearing potential (CBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 21 days after stopping the treatment.

Other inclusion/exclusion criteria may apply

Sources for eligibility
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  • Central Alabama ResearchBirmingham, United StatesRecruiting
  • Alaska Oncology and Hematology LLCAnchorage, United StatesRecruiting
  • Western Reg MC-COH PhoenixGoodyear, United StatesRecruiting
  • CARTI Cancer CenterLittle Rock, United StatesRecruiting
  • Beverly Hills Cancer CenterBeverly Hills, United StatesRecruiting
  • Onco Inst of Hope and InnovationCerritos, United StatesRecruiting
  • City of Hope National MedicalDuarte, United StatesRecruiting
  • Providence Medical FoundationFullerton, United StatesRecruiting
  • Los Angeles Cancer Network Good SamaritanLos Angeles, United StatesRecruiting
  • El Camino HospitalMountain View, United StatesRecruiting
  • Palo Alto Medical FoundationMountain View, United StatesRecruiting
  • UC Irvine Medical CenterOrange, United StatesRecruiting
  • Sutter Inst Medical ResearchSacramento, United StatesRecruiting
  • School Of MedicineSacramento, United StatesRecruiting
  • Sharp Rees Stealy Medical Group IncSan Diego, United StatesRecruiting
  • AdventHealth Medical Group Hematology and OncologyDenver, United StatesRecruiting
  • Rocky Mountain Cancer CentersDenver, United StatesRecruiting
  • Georgetown University Lombardi Cancer CenterWashington D.C., United StatesRecruiting
  • Medstar Washington Hospital CenterWashington D.C., United StatesRecruiting
  • AdventHealth Altamonte SpringsAltamonte Springs, United StatesRecruiting
  • Holy Cross HealthFort Lauderdale, United StatesRecruiting
  • Hialeah HospitalHialeah, United StatesRecruiting
  • Memorial Cancer InstituteHollywood, United StatesRecruiting
  • Jupiter Medical CenterJupiter, United StatesRecruiting
  • Ocala Research Institute, IncOcala, United StatesRecruiting

And 203 more, listed on the interactive page.

Sources for sites
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Other registry identifiers

  • 2022-503001-38-00
Sources for references
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Related records

Drugs (5)

Lead sponsors (1)

Conditions (1)

Targets (4)