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Trial record 1 of 1 for:    ACT16106
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Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer (AMEERA-4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04191382
Recruitment Status : Terminated (early discontinuation based on strategic sponsor decision not driven by any safety concerns)
First Posted : December 9, 2019
Results First Posted : June 29, 2022
Last Update Posted : June 29, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Amcenestrant (SAR439859)
Drug: Letrozole
Enrollment 105
Recruitment Details The study was conducted at 32 active sites in 8 countries. A total of 135 participants were screened from 04-February-2020 to 21-April-2021, of which 30 participants were screen failures mainly due to selection criteria not met.
Pre-assignment Details A total of 105 participants with early breast cancer were randomized in 1:1:1 ratio to receive treatment with amcenestrant 400 milligrams (mg), amcenestrant 200 mg, or letrozole 2.5 mg.
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14. Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14. Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Period Title: Overall Study
Started [1] 34 36 35
Treated 33 36 35
Completed 33 36 35
Not Completed 1 0 0
Reason Not Completed
Withdrawal by Subject             1             0             0
[1]
Randomized
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg Total Title
Hide Arm/Group Description Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14. Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14. Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14. [Not Specified]
Overall Number of Baseline Participants 34 36 35 105
Hide Baseline Analysis Population Description
Analysis was performed on intent-to-treat (ITT) population that included all enrolled participants for whom there was a confirmation of successful allocation of a randomization number by interactive response technology (IRT) and were analyzed according to the treatment arm assigned at randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 36 participants 35 participants 105 participants
62.4  (8.6) 63.4  (8.4) 63.7  (8.5) 63.2  (8.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 36 participants 35 participants 105 participants
Female
34
 100.0%
36
 100.0%
35
 100.0%
105
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 36 participants 35 participants 105 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   5.9%
3
   8.3%
5
  14.3%
10
   9.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.9%
0
   0.0%
0
   0.0%
1
   1.0%
White
23
  67.6%
24
  66.7%
25
  71.4%
72
  68.6%
More than one race
0
   0.0%
1
   2.8%
1
   2.9%
2
   1.9%
Unknown or Not Reported
8
  23.5%
8
  22.2%
4
  11.4%
20
  19.0%
Ki67 expression at Baseline   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of positive tumor cells
Number Analyzed 32 participants 36 participants 32 participants 100 participants
33.8  (16.3) 31.2  (14.3) 32.6  (18.5) 32.5  (16.3)
[1]
Measure Description: Tumor tissue collected through a core-cut biopsy at Baseline was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading.
[2]
Measure Analysis Population Description: Here, 'Number analyzed' signifies participants with available data at Baseline for the specified Baseline measure.
1.Primary Outcome
Title Percent Change From Baseline in Ki67 Level at Day 15
Hide Description 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.
Time Frame Baseline, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on modified intent-to-treat (mITT) population that included all enrolled participants for whom there was a confirmation of successful allocation of a randomization number by IRT, who had taken at least one study drug, and who had both Baseline and post treatment available biopsies with Ki67 values.
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description:
Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.
Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.
Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Overall Number of Participants Analyzed 31 35 29
Geometric Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
75.9
(67.9 to 81.9)
68.2
(58.4 to 75.7)
77.7
(70.0 to 83.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Amcenestrant 400 mg, Letrozole 2.5 mg
Comments Geometric LS-means ratio of proportional change was the ratio of geometric LS-means of the proportional change between groups (Amcenestrant 400 mg versus Letrozole 2.5 mg).
Type of Statistical Test Other
Comments Other descriptive analysis
Method of Estimation Estimation Parameter Ratio of Geometric Means
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.72 to 1.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Amcenestrant 200 mg, Letrozole 2.5 mg
Comments Geometric LS-means ratio of proportional change was the ratio of geometric LS-means of the proportional change between groups (Amcenestrant 200 mg versus Letrozole 2.5 mg).
Type of Statistical Test Other
Comments Other descriptive analysis
Method of Estimation Estimation Parameter Ratio of Geometric Means
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.95 to 2.12
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Percent Change From Baseline in Ki67 Greater Than or Equal to (>=) 50 Percent at Day 15
Hide Description 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.
Time Frame Baseline, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description:
Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.
Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.
Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Overall Number of Participants Analyzed 31 35 29
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
74.2
(55.4 to 88.1)
68.6
(50.7 to 83.1)
89.7
(72.6 to 97.8)
3.Secondary Outcome
Title Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at Day 15
Hide Description 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.
Time Frame Baseline, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description:
Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.
Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.
Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Overall Number of Participants Analyzed 28 32 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-176.7
(-201.4 to -152.0)
-202.9
(-226.1 to -179.7)
-32.5
(-57.2 to -7.7)
4.Secondary Outcome
Title Number of Participants With Abnormalities: Hematological Parameters
Hide Description 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.
Time Frame From first dose of study drug up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population that included all participants who were randomly assigned to study drug and who took at least 1 dose of study drug. Here, 'Number analyzed' signifies participants with available data for each specified category for this outcome measure.
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description:
Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.
Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.
Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Overall Number of Participants Analyzed 33 36 35
Measure Type: Count of Participants
Unit of Measure: Participants
White blood cell decreased Number Analyzed 32 participants 35 participants 35 participants
5
  15.6%
6
  17.1%
3
   8.6%
Neutrophil count decreased Number Analyzed 32 participants 35 participants 35 participants
1
   3.1%
0
   0.0%
1
   2.9%
Anemia (hemoglobin decreased) Number Analyzed 32 participants 35 participants 35 participants
6
  18.8%
4
  11.4%
1
   2.9%
Hemoglobin increased Number Analyzed 32 participants 35 participants 35 participants
0
   0.0%
0
   0.0%
0
   0.0%
Platelet count decreased Number Analyzed 32 participants 35 participants 35 participants
1
   3.1%
1
   2.9%
0
   0.0%
Lymphocyte count decreased Number Analyzed 32 participants 35 participants 35 participants
1
   3.1%
3
   8.6%
1
   2.9%
INR increased Number Analyzed 28 participants 28 participants 31 participants
0
   0.0%
0
   0.0%
0
   0.0%
Eosinophilia (eosinophils increased) Number Analyzed 32 participants 35 participants 35 participants
2
   6.3%
1
   2.9%
1
   2.9%
5.Secondary Outcome
Title Number of Participants With Abnormalities: Clinical Chemistry
Hide Description 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.
Time Frame From first dose of study drug up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population. Here, 'Number analyzed' signifies participants with available data for each specified category for this outcome measure.
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description:
Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.
Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.
Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Overall Number of Participants Analyzed 33 36 35
Measure Type: Count of Participants
Unit of Measure: Participants
Hypernatremia (sodium increased) Number Analyzed 32 participants 35 participants 35 participants
1
   3.1%
1
   2.9%
1
   2.9%
Hyponatremia (sodium decreased) Number Analyzed 32 participants 35 participants 35 participants
0
   0.0%
1
   2.9%
0
   0.0%
Hyperkalemia (potassium increased) Number Analyzed 32 participants 35 participants 35 participants
2
   6.3%
1
   2.9%
1
   2.9%
Hypokalemia (potassium decreased) Number Analyzed 32 participants 35 participants 35 participants
0
   0.0%
2
   5.7%
0
   0.0%
Creatinine increased Number Analyzed 32 participants 34 participants 35 participants
0
   0.0%
3
   8.8%
2
   5.7%
Hypoglycemia (glucose decreased) Number Analyzed 32 participants 35 participants 35 participants
0
   0.0%
1
   2.9%
0
   0.0%
Time Frame From first dose up to 30 days following the last dose of study drug (up to 45 days)
Adverse Event Reporting Description Reported adverse events (AEs) are treatment-emergent adverse events (TEAEs) i.e., AEs that developed, worsened, or became serious during the treatment period (time from the first dose of study drug up to 30 days after last dose of study drug). Analysis was performed on safety population.
 
Arm/Group Title Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Hide Arm/Group Description Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14. Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14. Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
All-Cause Mortality
Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/33 (0.00%)      0/36 (0.00%)      0/35 (0.00%)    
Hide Serious Adverse Events
Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/33 (0.00%)      2/36 (5.56%)      0/35 (0.00%)    
Infections and infestations       
Pneumonia  1  0/33 (0.00%)  0 1/36 (2.78%)  1 0/35 (0.00%)  0
Wound Infection  1  0/33 (0.00%)  0 1/36 (2.78%)  1 0/35 (0.00%)  0
1
Term from vocabulary, MedDRA24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Amcenestrant 400 mg Amcenestrant 200 mg Letrozole 2.5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/33 (33.33%)      12/36 (33.33%)      14/35 (40.00%)    
Gastrointestinal disorders       
Constipation  1  1/33 (3.03%)  1 2/36 (5.56%)  2 1/35 (2.86%)  1
Diarrhoea  1  0/33 (0.00%)  0 3/36 (8.33%)  3 3/35 (8.57%)  3
General disorders       
Asthenia  1  2/33 (6.06%)  2 2/36 (5.56%)  2 0/35 (0.00%)  0
Fatigue  1  2/33 (6.06%)  2 1/36 (2.78%)  1 1/35 (2.86%)  1
Feeling Cold  1  2/33 (6.06%)  2 0/36 (0.00%)  0 0/35 (0.00%)  0
Injury, poisoning and procedural complications       
Procedural Pain  1  2/33 (6.06%)  2 1/36 (2.78%)  1 2/35 (5.71%)  2
Investigations       
Alanine Aminotransferase Increased  1  1/33 (3.03%)  1 2/36 (5.56%)  2 0/35 (0.00%)  0
Metabolism and nutrition disorders       
Decreased Appetite  1  2/33 (6.06%)  2 1/36 (2.78%)  1 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  2/33 (6.06%)  2 0/36 (0.00%)  0 3/35 (8.57%)  3
Nervous system disorders       
Headache  1  3/33 (9.09%)  3 0/36 (0.00%)  0 2/35 (5.71%)  2
Psychiatric disorders       
Anxiety  1  1/33 (3.03%)  1 2/36 (5.56%)  2 0/35 (0.00%)  0
Insomnia  1  4/33 (12.12%)  4 1/36 (2.78%)  1 0/35 (0.00%)  0
Reproductive system and breast disorders       
Breast Pain  1  1/33 (3.03%)  1 0/36 (0.00%)  0 3/35 (8.57%)  3
Vascular disorders       
Hot Flush  1  4/33 (12.12%)  4 1/36 (2.78%)  1 5/35 (14.29%)  5
1
Term from vocabulary, MedDRA24.0
Indicates events were collected by systematic assessment
The study recruitment discontinued early based on strategic sponsor decision that was not driven by any safety concerns. No inferential statistical analysis was performed due to early termination.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi aventis recherche & développement
Phone: 800-633-1610 ext 6#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04191382    
Other Study ID Numbers: ACT16106
2019-002015-26 ( EudraCT Number )
U1111-1228-9473 ( Other Identifier: UTN )
First Submitted: December 5, 2019
First Posted: December 9, 2019
Results First Submitted: May 27, 2022
Results First Posted: June 29, 2022
Last Update Posted: June 29, 2022