Clinical Trials /

Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer

NCT04059484

Description:

Primary Objective: To determine whether amcenestrant per os improves progression free survival (PFS) when compared with a 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

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of SAR439859 Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer (AMEERA-3)
  • Official Title: An Open Label Randomized Phase 2 Trial of SAR439859, Versus Endocrine Monotherapy as Per Physician's Choice in Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormonal Therapies (AMEERA-3)

Clinical Trial IDs

  • ORG STUDY ID: ACT16105
  • SECONDARY ID: 2018-004593-98
  • NCT ID: NCT04059484

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
SAR439859SAR439859
FulvestrantFaslodex®Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator
AnastrozoleArimidex®/Anastrozole GenericsFulvestrant/Aromatase inhibitors/Estrogen receptor modulator
LetrozoleFemara®/Letrozole GenericsFulvestrant/Aromatase inhibitors/Estrogen receptor modulator
ExemestaneAromasin®/Exemestane GenericsFulvestrant/Aromatase inhibitors/Estrogen receptor modulator
TamoxifenNolvadex®/Tamoxifen GenericsFulvestrant/Aromatase inhibitors/Estrogen receptor modulator

Purpose

Primary Objective: To determine whether SAR439859 per os improves progression free survival (PFS) when compared with a 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 SAR439859 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.

Detailed Description

      The duration of the study for an individual participant will include a period to assess
      eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1
      cycle (28 days of study treatment), and an end of treatment (EOT) visit at least 30 days (or
      until the participant receive another anticancer therapy, whichever is earlier) following the
      last administration of study treatment. Study treatment may continue until precluded by
      unacceptable toxicity, disease progression, death or upon participant's request.

      An extension of recruitment for Chinese participants is planned in this study: After
      completion of randomization in the global part of the study, randomization will continue in
      China until approximately 90 Chinese participants are randomized.
    

Trial Arms

NameTypeDescriptionInterventions
SAR439859ExperimentalDaily SAR439859 dose administered orally under fed or fast condition
  • SAR439859
Fulvestrant/Aromatase inhibitors/Estrogen receptor modulatorActive ComparatorControl treatment of the choice of the physician depending on each participant's medical condition and in accordance with the approved label may include 1 of the following treatments used as monotherapy. Fulvestrant Aromatase inhibitors (anastrozole, letrozole, exemestane) Selective estrogen receptor modulator (Tamoxifen)
  • Fulvestrant
  • Anastrozole
  • Letrozole
  • Exemestane
  • Tamoxifen

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.

          -  ER positive status.

          -  HER2 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 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 SAR439859. 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 >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
             least3 months before randomization.

          -  Treatment with drugs that have the potential to inhibit UGT less than 2 weeks before
             randomization .

          -  Treatment with strong or moderate CYP3A/CYP2C8 inducers within 2 weeks before
             randomization.

          -  Ongoing treatment with drugs that are substrate of P-glycoprotein (P gp) (dabigatran,
             digoxin, fexofenadine).

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:Up to 18 months after the first randomized participant
Safety Issue:
Description:PFS is defined as the time interval from the date of randomization to the date of documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever comes first.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Up to 64 months after the first randomized participant
Safety Issue:
Description:OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
Measure:Objective Response Rate (ORR)
Time Frame:Up to 18 months after the first randomized participant
Safety Issue:
Description:ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), as best overall response determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
Measure:Disease Control Rate (DCR)
Time Frame:Up to 18 months after the first randomized participant
Safety Issue:
Description:DCR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 18 months after the first randomized participant
Safety Issue:
Description:CBR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
Measure:Duration of Response (DOR)
Time Frame:Up to 18 months after the first randomized participant
Safety Issue:
Description:DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by objective radiographic disease assessment per RECIST 1.1 or death from any cause, whichever occurs first.
Measure:PFS according to (ESR1) mutation status
Time Frame:Up to 18 months after the first randomized participant
Safety Issue:
Description:PFS as per the estrogen receptor 1 (ESR1) mutation status determined at study entry.
Measure:Assessments of the Pharmacokinetic (PK) parameter of SAR439859 as single agent: Plasma Concentrations
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of cycles 3, 4 and 6 (each cycle is 28 days)
Safety Issue:
Description:SAR439859 plasma concentrations.
Measure:Patient Reported Outcome (PRO) - health-related quality of life and health status using the European Quality of Life-5 Dimensions (EQ-5D)
Time Frame:Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days)
Safety Issue:
Description:EQ-5D is a standardized measure of health status.
Measure:Patient Reported Outcome (PRO) - the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC-QLQ-C30)
Time Frame:Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days)
Safety Issue:
Description:The EORTC-QLQ-C30 is composed of both multi item scales and single item measures. These include 5 functional scales, 3 symptom scales, a Global Health Status (GHS)/quality of life scale, and 6 single items.
Measure:Patient Reported Outcome (PRO) - EORTC-QLQ breast cancer (EORTC-QLQ-BR23)
Time Frame:Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days)
Safety Issue:
Description:The EORTC-QLQ-BR23 contains 23 items: 8 assessing function and 15 items assessing symptoms of disease or treatment.
Measure:Overall safety profile - Treatment-Emergent Adverse events
Time Frame:Evaluated continuously throughout study from the date of enrollment, up to 30 days after last study treatment administration
Safety Issue:
Description:Number of participants with treatment-emergent adverse events (TEAEs).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

January 26, 2021