Clinical Trials /

Phase 2 Window Study of SAR439859 Versus Letrozole in ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer (AMEERA-4)

NCT04191382

Description:

Primary Objective: To determine whether SAR439859 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

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Window Study of SAR439859 Versus Letrozole in ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer
  • Official Title: Phase 2 Window Study of Two Dose Levels of 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

  • Breast Cancer

Interventions

DrugSynonymsArms
SAR439859SAR439859 dose regimen 1
letrozoleletrozole

Purpose

Primary Objective: To determine whether SAR439859 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

NameTypeDescriptionInterventions
SAR439859 dose regimen 1ExperimentalSAR439859 dose regimen 1 administered for 14 days
  • SAR439859
SAR439859 dose regimen 2ExperimentalSAR439859 dose regimen 2 administered for 14 days
  • SAR439859
letrozoleActive Comparatorletrozole 2.5 mg administered once daily for 14 days
  • letrozole

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

          -  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 or moderate Cytochrome P450 3A (CYP3A), CYP2C8 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

          -  Ongoing treatment with drugs that are sensitive substrates of P-glycoprotein (P-gp)

          -  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:Recruiting
Lead Sponsor:Sanofi

Last Updated

March 19, 2020