Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer
Condition: Breast Cancer Metastatic
MeSH terms: Breast Neoplasms
Intervention: Amcenestrant; Fulvestrant; Anastrozole; Letrozole; Exemestane; Tamoxifen
Intervention description: Pharmaceutical form: Capsule
Route of administration: Oral; Pharmaceutical form: Solution for injection
Route of administration: Intramuscular; Pharmaceutical form:Tablets or capsules
Route of administration: Oral; Pharmaceutical form: Tablets or capsules
Route of administration: Oral; Pharmaceutical form: Tablets or capsules
Route of administration: Oral; Pharmaceutical form: Tablets or capsules
Route of administration: Oral
Intervention MeSH terms: Tamoxifen; Letrozole; Fulvestrant; Anastrozole; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 367.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To determine whether amcenestrant per overall survival (os) improves progression free
      survival (PFS) when compared with an endocrine monotherapy of the choice of the physician, in
      participants with metastatic or locally advanced breast cancer

      Secondary Objectives:

        -  To compare the overall survival in the 2 treatment arms

        -  To assess the objective response rate in the 2 treatment arms

        -  To evaluate the disease control rate in the 2 treatment arms

        -  To evaluate the clinical benefit rate in the 2 treatment arms

        -  To evaluate the duration of response in the 2 treatment arms

        -  To evaluate the PFS according to the estrogen receptor 1 gene (ESR1) mutation status in
           the 2 treatment arms

        -  To evaluate the pharmacokinetics of amcenestrant as single agent

        -  To evaluate health-related quality of life in the 2 treatment arms

        -  To compare the overall safety profile in the 2 treatment arms
    

Eligibility criteria:

        Inclusion criteria :

          -  18 years or older.

          -  Histological or cytological diagnosis of adenocarcinoma of the breast.

          -  Locally advanced not amenable to radiation therapy or surgery in a curative intent,
             and/or metastatic disease.

          -  Estrogen receptor(ER) positive status.

          -  Human epidermal growth factor receptor 2 negative status.

          -  Participants must have received no more than 1 prior chemotherapeutic or 1 targeted
             therapy regimen for advanced/metastatic disease.

          -  In the main study, a prior treatment with a Cyclin-dependent kinase 4 and 6(CDK 4/6)
             inhibitor is mandatory if this treatment is approved and can be reimbursed for this
             participant. The percentage of participants without previous CDK 4/6 inhibitor will be
             capped to 20%. In the Chinese extension cohort, previous treatment with a CDK 4/6
             inhibitor will not be mandatory, and there will be no limitation to the number of
             participants naïve to CDK4/6 inhibitor.

          -  Participants must present a secondary endocrine resistance to endocrine therapy
             defined as: progression while on endocrine therapy after at least 6 months of
             treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy
             but after the first 2 years, or with a relapse within 12 months after completing
             adjuvant endocrine therapy.

          -  Male or Female.

        Exclusion criteria:

          -  Eastern Cooperative Oncology Group performance status =>2.

          -  Medical history or ongoing gastrointestinal disorders potentially affecting the
             absorption of amcenestrant. Participants unable to swallow normally and to take
             capsules.

          -  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 greater than 3 years are allowed.

          -  Severe uncontrolled systemic disease at screening .

          -  Participants with known brain metastases that are untreated, symptomatic or require
             therapy to control symptoms.

          -  Prior treatment with mammalian target of rapamycin inhibitors or any other selective
             estrogen receptor degrader(SERD) compound, except fulvestrant if stopped for at least
             3 months before randomization.

          -  Treatment with drugs that have the potential to inhibit Uridine'5
             Diphospho-Glucuronosyl Transferase(UGT) less than 2 weeks before randomization.

          -  Treatment with strong Cytochrome P450 (CYP)3A inducers within 2 weeks before
             randomization.

          -  Ongoing treatment with drugs that are sensitive substrate of organic anion
             transporting polypeptide 1B1/B3(OATP1B1/B3) (asunaprevir, atorvastatin, bosentan,
             danoprevir, fexofenadine, glyburide, nateglinide, pitavastatin, pravastatin,
             replaglinide, rosuvastatin, and simvastatin acid).

          -  Treatment with anticancer agents (including investigational drugs) less than 3 weeks
             before randomization.

          -  Inadequate hematological, coagulation, renal and liver functions.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.