Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer
- Registration Number
- NCT04191382
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To determine whether amcenestrant given at 2 different doses improved the antiproliferative activity when compared to letrozole.
Secondary Objectives:
* To assess the proportion of participants with a relative decrease from Baseline in percentage of positive tumor cells tested by immunohistochemistry greater than or equal to (\>=) 50 percent (%) (Ki67 \>=50%) in the three treatment arms.
* To assess estrogen receptor (ER) degradation in biopsies in participants in the three treatment arms.
* To assess safety in the three treatment arms.
- Detailed Description
Duration of the study, per participant, would include screening period of up to 14 days before randomization, treatment period of 14 days and post-treatment safety follow-up period of 30±7 days after last investigational medicinal product (IMP) intake.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 105
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Amcenestrant 400 mg Amcenestrant (SAR439859) Participants received 4 capsules of 100 milligrams (mg) of amcenestrant once daily (QD) from Day 1 to Day 14. Amcenestrant 200 mg Amcenestrant (SAR439859) Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14. Letrozole 2.5 mg Letrozole Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Ki67 Level at Day 15 Baseline, Day 15 Tumor tissue collected through a core-cut biopsy at Baseline and Day 15 was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading. Ki67 percent change from Baseline for a given participant was defined as 100\*(Ki67pre - Ki67post) / Ki67pre, where Ki67pre and Ki67post were pre-treatment and post-treatment Ki67 value of the participant. Adjusted geometric least square (LS) means and 95 percentage (%) confidence interval (CI) for the percent change were obtained from analysis of covariance (ANCOVA) model of the log proportional change i.e., log (Ki67post/ki67pre) with treatment and log-Ki67pre as fixed effect and converted by antilog transformation.
- Secondary Outcome Measures
Name Time Method Number of Participants With Abnormalities: Hematological Parameters From first dose of study drug up to Day 14 Hematology parameters covered by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and included: Hemoglobin, Lymphocyte, Neutrophils, Leukocytes (white blood cells), Anemia, Platelets, Eosinophils, and international normalized ratio (INR). An NCI-CTCAE Grades 1 to 5 were described as: Grade 1-Mild; asymptomatic/mild symptoms; Grade 2-Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental daily activities. Grade 3-Severe/medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4-Life-threatening consequences; Grade 5-Death. Data for 'All Grades' were reported in this outcome measure.
Percentage of Participants With Percent Change From Baseline in Ki67 Greater Than or Equal to (>=) 50 Percent at Day 15 Baseline, Day 15 Tumor tissue collected through a core-cut biopsy at Baseline and Day 15 was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading. Ki67 percent change from Baseline for a given participant was defined as 100\*(Ki67pre - Ki67post) / Ki67pre, where Ki67pre and Ki67post were pre-treatment and post-treatment Ki67 value of the participant.
Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at Day 15 Baseline, Day 15 Change from Baseline in ER expression was measured by H-Score. The H-score was calculated as the sum of the percent of cells staining positive (0 to 100) multiplied staining intensity level from 0 to 3 (0=none, 1=low, 2=moderate, 3=high). Total ER expression H-score ranged from 0 to 300, where higher score indicated stronger ER expression. Change from Baseline in H-Score equals H-scorepost minus H-scorepre; where H-scorepost and H-scorepre denoted post-treatment and pre-treatment H-scores, respectively. LS-means and 95% CI were obtained from an ANCOVA model for change from baseline with treatment and baseline as fixed effect.
Number of Participants With Abnormalities: Clinical Chemistry From first dose of study drug up to Day 14 Clinical chemistry laboratory parameters covered by NCI-CTCAE and included: Glucose, Potassium, Sodium, Creatinine. An NCI-CTCAE Grades 1 to 5 were described as: Grade 1-Mild; asymptomatic or mild symptoms; Grade 2- Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental daily activities; Grade 3-Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4-Life-threatening consequences; Grade 5-Death. Data for 'All Grades' were reported in this outcome measure.
Trial Locations
- Locations (32)
Investigational Site Number 8400010
🇺🇸Los Angeles, California, United States
Investigational Site Number 8400005
🇺🇸Lincoln, Nebraska, United States
Investigational Site Number 8400012
🇺🇸Tacoma, Washington, United States
Investigational Site Number 0560002
🇧🇪Namur, Belgium
Investigational Site Number 8400014
🇺🇸Tucson, Arizona, United States
Investigational Site Number 8400018
🇺🇸Fort Wayne, Indiana, United States
Investigational Site Number 2500004
🇫🇷Paris, France
Investigational Site Number 8040004
🇺🇦Kharkiv, Ukraine
Investigational Site Number 3800004
🇮🇹Meldola, Italy
Investigational Site Number 3800002
🇮🇹Milano, Italy
Investigational Site Number 6430003
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 8400016
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 3920003
🇯🇵Sapporo-Shi, Japan
Investigational Site Number 7240001
🇪🇸Madrid, Spain
Investigational Site Number 0560001
🇧🇪Leuven, Belgium
Investigational Site Number 6430006
🇷🇺Moscow, Russian Federation
Investigational Site Number 2500001
🇫🇷Nantes, France
Investigational Site Number 3920001
🇯🇵Yokohama-Shi, Japan
Investigational Site Number 8040001
🇺🇦Uzhgorod, Ukraine
Investigational Site Number 3800001
🇮🇹Milano, Italy
Investigational Site Number 6430002
🇷🇺Saint -Petersburg, Russian Federation
Investigational Site Number 8400007
🇵🇷Hato Rey, Puerto Rico
Investigational Site Number 3920002
🇯🇵Osaka-Shi, Japan
Investigational Site Number 6430007
🇷🇺St.Petersburg, Russian Federation
Investigational Site Number 7240002
🇪🇸Valencia / Valencia, Spain
Investigational Site Number 2500003
🇫🇷Toulouse Cedex 9, France
Investigational Site Number 7240003
🇪🇸Córdoba, Spain
Investigational Site Number 6430004
🇷🇺Moscow, Russian Federation
Investigational Site Number 2500002
🇫🇷Saint Cloud, France
Investigational Site Number 7240005
🇪🇸Barcelona, Spain
Investigational Site Number 8040005
🇺🇦Zaporizhzhya, Ukraine
Investigational Site Number 8040002
🇺🇦Vinnytsia, Ukraine