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

• Status: Terminated
• Trial end date: 2021-05-28
• Target enrollment: 0
• Participant gender: Female

Summary

Primary Objective:

To determine whether amcenestrant 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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Letrozole

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

• 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 has been disease free for >3 years are allowed

• Evidence of metastatic spread by standard assessment according to local practice

• Treatment with strong Cytochrome P450 3A (CYP3A) 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

• Treatment with drugs that are 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 is longer.

• 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.