Description:
Primary Objective:
To determine whether amcenestrant given at 2 different doses improves 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 ≥50% (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
Title
- Brief Title: Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer
- Official Title: Phase 2 Window Study of Two Dose Levels of Amcenestrant [SAR439859] (SERD) Versus Letrozole in Newly Diagnosed Pre-operative Post-menopausal Patients With ER Positive, HER2 Negative Primary Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
ACT16106
- SECONDARY ID:
2019-002015-26
- SECONDARY ID:
U1111-1228-9473
- NCT ID:
NCT04191382
Conditions
Interventions
Drug | Synonyms | Arms |
---|
amcenestrant (SAR439859) | | SAR439859 dose regimen 1 |
letrozole | | letrozole |
Purpose
Primary Objective:
To determine whether amcenestrant given at 2 different doses improves 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 ≥50% (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 patient, will 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.
Trial Arms
Name | Type | Description | Interventions |
---|
SAR439859 dose regimen 1 | Experimental | SAR439859 dose regimen 1 administered for 14 days | |
SAR439859 dose regimen 2 | Experimental | SAR439859 dose regimen 2 administered for 14 days | |
letrozole | Active Comparator | letrozole 2.5 mg administered once daily for 14 days | |
Eligibility Criteria
Inclusion criteria :
- Histological or cytological proven diagnosis of invasive breast adenocarcinoma
- Localized breast cancer eligible for upfront breast conservative surgery or upfront
mastectomy: Stage I, Stage II or operable Stage III (excludes T4) as defined in
American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition 2017
- Postmenopausal women as defined by one of the following:
- Spontaneous cessation of menses >12 months;
- or who have received hormonal replacement therapy but have discontinued this treatment
and have follicle stimulating hormone (FSH) level in the postmenopausal range;
- or with status post bilateral surgical oophorectomy;
- or post bilateral ovarian ablation through pelvic radiotherapy
- Breast tumor size of at least 10 mm in greatest dimension measured by ultrasound
- Primary tumor must be positive for Estrogen Receptors (ER+) and negative for HER2
(HER2-) receptor by immunohistochemistry
- Ki67 level of at least 15% at diagnosis from immunohistochemistry of the tumor
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Exclusion criteria:
- Medical history or ongoing gastrointestinal disorders potentially affecting the
absorption of SAR439859 or letrozole; Participants unable to swallow normally and to
take capsules or tablets
- Participants with known active hepatitis A, B, C infection; or hepatic cirrhosis.
- Participant with any other cancer; adequately treated basal cell or squamous cell skin
cancer or in situ cervical cancer or any other cancer from which the participant has
been disease free for >3 years are allowed
- Evidence of metastatic spread by standard assessment according to local practice
- Treatment with strong Cytochrome P450 3A (CYP3A) inducers or drugs that have the
potential to inhibit uridine diphosphate glucuronosyltransferase (UGT) within 2 weeks
before first study treatment administration or 5 elimination half-lives whichever is
longest
- Treatment with drugs that are sensitive substrates of P-glycoprotein (P-gp) or of
breast cancer resistance protein (BCRP) within 2 weeks before first study treatment
administration or 5 elimination half-lives whichever is longer.
- Use of any investigational agent within 4 weeks prior to randomization
- Recent use of hormone replacement therapy (last dose ≤30 days prior to randomization)
- Prior anti-cancer treatment is not allowed unless it was completed at least 1 year
prior to inclusion into this trial
- Previous systemic or local treatment for the new primary breast cancer currently under
investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
- Inadequate hematological or renal function
- Prothrombin time/international normalized ratio (INR) >1.5 x ULN or outside
therapeutic range if receiving anticoagulation that would affect the prothrombin
time/INR
- Any of the following abnormal liver function test results: Aspartate aminotransferase
>1.5 x upper limit of normal (ULN); Alanine aminotransferase >1.5 x ULN; Total
bilirubin >1.5 x ULN
- Participants are employees of the clinical study site or other individuals directly
involved in the conduct of the study, or immediate family members of such individuals
- Sensitivity to any of the study interventions, or components thereof, or drug or other
allergy that, in the opinion of the Investigator, contraindicates participation in the
study
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Ki67 |
Time Frame: | Baseline and Day 15 |
Safety Issue: | |
Description: | Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry) after a 14-day treatment period compared to baseline assessed by central reading |
Secondary Outcome Measures
Measure: | Ki67≥50% |
Time Frame: | Baseline and Day 15 |
Safety Issue: | |
Description: | Proportion of participants with relative change from baseline in Ki67≥50% after a 14-day treatment period compared to baseline |
Measure: | ER Expression |
Time Frame: | Baseline and Day 15 |
Safety Issue: | |
Description: | Change in ER expression after a 14-day treatment period compared to baseline |
Measure: | Adverse Events (AEs)/Serious Adverse Events (SAEs) |
Time Frame: | Up to approximately Day 44 |
Safety Issue: | |
Description: | Percentage of participants with AEs/SAEs |
Measure: | Clinical Laboratory Test Abnormalities |
Time Frame: | Up to Day 14 |
Safety Issue: | |
Description: | Percentage of participants with clinical laboratory test abnormalities |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Sanofi |
Last Updated
June 29, 2021