Phase IIIb Study of Ribociclib + ET in Early Breast Cancer

Early Breast Cancer Clinical Trial

— Adjuvant WIDER  

Official title:

A Phase IIIb Study to Characterize the Effectiveness and Safety of Adjuvant Ribociclib in a Wide Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05827081
• Other study ID #: CLEE011O12001
• Status: Suspended
• Phase: Phase 3
• Start date: February 28, 2024
• Est. completion date: September 20, 2030

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An open-label, multicenter, phase IIIb, single-arm study to evaluate the safety and efficacy of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a wide patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, II (subset) or I (high-risk subset as exploratory cohort) early Breast Cancer (EBC)

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 3100
• Est. completion date: September 20, 2030
• Est. primary completion date: September 7, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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 enrollment should occur within 36 months of prior ET start date and the participant should have at least 3 years remaining of endocrine adjuvant therapy. For participants with prior ET treatment > 12 months, the investigator should rule out disease recurrence prior to enrollment. The number of participants with prior ET between 12 and 36 months will be capped at 1000.

• Participant has no contraindication for the adjuvant ET in the study.

• Participant after complete surgical resection with the final surgical specimen microscopic margins free from tumor and in one of below categories:

• Anatomic Stage Group III

• Anatomic Stage Group II (subset)

• Anatomic Stage Group I (high-risk subset as exploratory cohort)

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

• Participant has adequate bone marrow and organ function.

Key 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.

Other inlcusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Breast Cancer

Intervention

Drug:
• Ribociclib
Ribociclib 400 mg orally once daily on days 1-21 of a 28 day cycle followed by 7 days rest
• Letrozole
Letrozole 2.5 mg orally once daily continuously
• Ansastrozole
Anastrozole 1 mg orally once daily continuously.
• Goserelin
Goserelin administered 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
• Leuprolide
Leuprolide administered 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
• Exemestane
Exemestane 25 mg once daily continuously

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Gateshead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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.	At 3 years
Secondary	Invasive Disease-Free Survival (iDFS)	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.	Up to approximately 6 years
Secondary	Distant Relapse-Free Survival (DRFS)	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.	Up to approximately 6 years
Secondary	Recurrence-Free Interval (RFI)	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.	Up to approximately 6 years
Secondary	Relative dose intensity (RDI) of ribociclib	RDI is defined as the ratio of the dose intensity delivered to the planned dose intensity.	Up to 3 years
Secondary	Overall Survival (OS)	OS is defined as time from the start of study treatment to date of death due to any cause.	Up to approximately 6 years
Secondary	Time To Discontinuation (TTD) of ribociclib	TTD is defined as the time from starting ribociclib to the time to treatment discontinuation due to any cause.	Up to 3 years
Secondary	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 approximately 6 years
Secondary	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 approximately 6 years
Secondary	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 approximately 6 years
Secondary	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 approximately 6 years
Secondary	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 approximately 6 years