This is a Phase III, global, randomized, open-label, multicenter, study evaluating the efficacy and safety of adjuvant giredestrant compared with physician's choice of endocrine therapy in participants with medium- and high-risk Stage I-III histologically confirmed estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4,170
Giredestrant 30 milligrams (mg) will be administered orally once a day (QD) on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first).
The physician's choice of endocrine therapy (PCET) is limited to tamoxifen or one of the specified third generation aromatase inhibitors: letrozole, anastrozole, or exemestane. Participants will receive PCET daily on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first). Continuing PCET after 5 years is at the discretion of the investigator and per local standard of care. Dose administration of PCET should be performed in accordance with the local prescribing information for the respective product.
A luteinizing hormone-releasing hormone (LHRH) agonist will be administered to male participants and premenopausal/perimenopausal participants according to local prescribing information. The investigator may determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.
Southern Cancer Center
Daphne, Alabama, United States
CBCC Global Research Inc., at Comprehensive Blood and Cancer Center
Bakersfield, California, United States
St Joseph Heritage Healthcare
Fullerton, California, United States
Long Beach Memorial Medical Center
Long Beach, California, United States
Cancer Blood and Specialty Clinic
Los Alamitos, California, United States
Invasive Disease-Free Survival (IDFS), Excluding Second Primary Non-Breast Cancers
Time frame: From randomization to first occurrence of an IDFS event (up to 10 years)
Overall Survival
Time frame: From randomization to death from any cause (up to 10 years)
Invasive Disease-Free Survival (IDFS), Including Second Primary Non-Breast Cancers
Time frame: From randomization to first occurrence of an IDFS event (up to 10 years)
Disease-Free Survival (DFS)
Time frame: From randomization to first occurrence of a DFS event (up to 10 years)
Distant Recurrence-Free Interval (DRFI)
Time frame: From randomization to first occurrence of a DFRI event (up to 10 years)
Locoregional Recurrence-Free Interval (LRRFI)
Time frame: From randomization to first occurrence of a LRRFI event (up to 10 years)
Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Change from Baseline in the Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Change from Baseline in the Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Change from Baseline in the Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Change from Baseline in the EQ 5D-5L Index-Based Score at Specified Timepoints
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Change from Baseline in the EQ 5D-5L Visual Analogue Scale (VAS) Score at Specified Timepoints
Time frame: Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years)
Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)
Time frame: From start of treatment until 28 days after the final dose of study treatment (up to 5 years)
Plasma Concentrations of Giredestrant at Specified Timepoints
Time frame: Predose and 3-4 hours postdose on Day 1 of Cycles 1 and 2, and predose on Day 1 of Cycles 3 and 6 (1 cycle is 28 days)
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The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
Orange, California, United States
Kaiser Permanente - San Diego
San Diego, California, United States
Sansum Clinic
Santa Barbara, California, United States
UCLA Hematology/Oncology
Santa Monica, California, United States
Torrance Memorial Physician Network/Cancer Care
Torrance, California, United States
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