Clinical Trials /

Phase 2 Study of SAR439859 Versus Physician's Choice in Premenopausal and Postmenopausal Locally Advanced or Metastatic ER-positive Breast Cancer

NCT04059484

Description:

Primary Objective: To determine whether SAR439859 per 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 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 overall survival 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 evaluate 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 Premenopausal and Postmenopausal Locally Advanced or Metastatic ER-positive Breast Cancer
  • Official Title: An Open Label Randomized Phase 2 Trial of SAR439859, Versus Endocrine Monotherapy as Per Physician's Choice in Premenopausal and Postmenopausal Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormonal Therapies

Clinical Trial IDs

  • ORG STUDY ID: ACT16105
  • SECONDARY ID: 2018-004593-98
  • SECONDARY ID: U1111-1217-2774
  • NCT ID: NCT04059484

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
SAR439859SAR439859
Endocrine monotherapy as per physician choiceControl treatment

Purpose

Primary Objective: To determine whether SAR439859 per 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 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 overall survival 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 evaluate 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.
    

Trial Arms

NameTypeDescriptionInterventions
SAR439859ExperimentalDaily SAR439859 dose administered orally
  • SAR439859
Control treatmentActive ComparatorEndocrine monotherapy as per physician choice
  • Endocrine monotherapy as per physician choice

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

          -  For patients with tumor accessible for paired biopsy at study entry: baseline samples,
             formalin fixed paraffin embedded (FFPE) archived biopsy samples (within 3 months prior
             initiation of study treatment) can be used, but preferably fresh biopsies from primary
             tumor or recurrence or metastasis, will be collected.

          -  Participants must have received no more than 1 prior chemotherapeutic or 1 targeted
             therapy regimen for advanced/metastatic disease.

          -  Participants must have progressed after at least 6 months of a continuous prior
             endocrine therapy for advanced breast cancer

          -  Participants must be postmenopausal women,

        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 bone-only metastasis .

          -  Participants with known brain metastases that are untreated, symptomatic or require
             therapy to control symptoms.

          -  Prior treatment with any other selective estrogen receptor degrader (SERD) compound,
             except fulvestrant if stopped for at least3 months before randomization.

          -  Treatment with antiviral agents, antifungal, and antioxidant agents less than 2 weeks
             before randomization .

          -  Treatment with strong or moderate CYP3A 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:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:Up to 17 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:Objective Response Rate (ORR)
Time Frame:Up to 17 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 17 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 17 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 17 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 17 months after the first randomized participant
Safety Issue:
Description:PFS as per the estrogen receptor 1 (ESR1) mutation status determined at study entry.
Measure:Overall Survival (OS)
Time Frame:Up to 35 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:Assessments of the Pharmacokinetic (PK) parameter of SAR439859: Plasma Concentrations
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of subsequent cycle every 2 cycles up to to 30 days after last study treatment (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 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 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 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:Not yet recruiting
Lead Sponsor:Sanofi

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