Clinical trial NCT05827081: Phase IIIb Study of Ribociclib + ET in Early Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Early Breast Cancer
Keywords: Hormone receptor positive (HR+)
Human epidermal growth factor receptor-2 negative (HER2-)
Early breast cancer (EBC)
premenopausal
postmenopausal
male breast cancer
ribociclib
LEE011
Endocrine therapy (ET)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-04-24
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

* Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC).
* 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 participants should have at least 3 years remaining of endocrine adjuvant therapy.
* 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.
* 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

Primary outcomes:
measure: Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years
timeFrame: At 3 years
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs) using CTCAE v4.03
timeFrame: Up to approximately 6 years
measure: Invasive Disease-Free Survival (iDFS)
timeFrame: Up to approximately 6 years
measure: Distant Disease-Free Survival (DDFS)
timeFrame: Up to approximately 6 years
measure: Distant Relapse-Free Survival (DRFS)
timeFrame: Up to approximately 6 years
measure: Recurrence-Free Interval (RFI)
timeFrame: Up to approximately 6 years
measure: Relative dose intensity (RDI) of ribociclib
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 6 years
measure: Time To Discontinuation (TTD) of ribociclib
timeFrame: Up to 3 years
measure: Changes from baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) score
timeFrame: Up to approximately 6 years
measure: Changes from baseline in Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) score
timeFrame: Up to approximately 6 years
measure: Changes from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score
timeFrame: Up to approximately 6 years
measure: Changes from baseline in European Quality of Life-5 Dimensions (EQ-5D-5L) score
timeFrame: Up to approximately 6 years
measure: Changes from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI-GH) score
timeFrame: Up to approximately 6 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology LLC
state: Alaska
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Ocala
country: United States
facility: Ocala Research Institute, Inc
state: Florida
city: Savannah
country: United States
facility: Summit Cancer Care PC
state: Georgia
city: Hinsdale
country: United States
facility: Hope And Healing Care
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Jackson
country: United States
facility: Jackson Oncology Associates
state: Mississippi
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
city: Gateshead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Antalya
country: Turkey
facility: Novartis Investigative Site
city: Cankaya Ankara
country: Turkey
facility: Novartis Investigative Site
city: Diyarbakir
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: