Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Amcenestrant (SAR439859); Letrozole
Intervention description: Pharmaceutical form: Capsules, Route of administration: Oral; Pharmaceutical form: Tablets, Route of administration: Oral
Intervention MeSH terms: Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 105.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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 (excluded 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 greater than (>) 12 months.

          -  or who had received hormonal replacement therapy but had discontinued the treatment
             and had 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 millimeters (mm) in greatest dimension measured by
             ultrasound.

          -  Primary tumor had to 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 had
             been disease free for >3 years were allowed.

          -  Evidence of metastatic spread by standard assessment according to local practice.

          -  Treatment with strong Cytochrome P450 3A (CYP3A) inducers or drugs that had the
             potential to inhibit uridine diphosphate glucuronosyltransferase (UGT) within 2 weeks
             before first study treatment administration or 5 elimination half-lives whichever was
             longest.

          -  Treatment with drugs that were 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 was longer.

          -  Use of any investigational agent within 4 weeks prior to randomization.

          -  Recent use of hormone replacement therapy (last dose less than or equal to [<=] 30
             days prior to randomization).

          -  Prior anti-cancer treatment was not allowed unless it was then 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 * upper limit of normal
             (ULN) or outside therapeutic range if received anticoagulation that would have had
             affected the prothrombin time/INR.

          -  Any of the following abnormal liver function test results: Aspartate aminotransferase
             >1.5 * ULN; Alanine aminotransferase >1.5 * ULN; Total bilirubin >1.5 * ULN.

          -  Participants were 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 was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.