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

Sanofi

Status and phase: Terminated; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Letrozole; Drug: Amcenestrant (SAR439859)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04191382

2019-002015-26 (EudraCT Number)

ACT16106

U1111-1228-9473 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To determine whether amcenestrant given at 2 different doses improved 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 greater than or equal to (>=) 50 percent (%) (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.

Full description

Duration of the study, per participant, would 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.

Enrollment: 105 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 (excluded 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 greater than (>) 12 months.
• or who had received hormonal replacement therapy but had discontinued the treatment and had 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 millimeters (mm) in greatest dimension measured by ultrasound.
• Primary tumor had to 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 had been disease free for >3 years were allowed.
• Evidence of metastatic spread by standard assessment according to local practice.
• Treatment with strong Cytochrome P450 3A (CYP3A) inducers or drugs that had the potential to inhibit uridine diphosphate glucuronosyltransferase (UGT) within 2 weeks before first study treatment administration or 5 elimination half-lives whichever was longest.
• Treatment with drugs that were 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 was longer.
• Use of any investigational agent within 4 weeks prior to randomization.
• Recent use of hormone replacement therapy (last dose less than or equal to [<=] 30 days prior to randomization).
• Prior anti-cancer treatment was not allowed unless it was then 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 * upper limit of normal (ULN) or outside therapeutic range if received anticoagulation that would have had affected the prothrombin time/INR.
• Any of the following abnormal liver function test results: Aspartate aminotransferase >1.5 * ULN; Alanine aminotransferase >1.5 * ULN; Total bilirubin >1.5 * ULN.
• Participants were 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 was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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105 participants in 3 patient groups

Amcenestrant 400 mg

Experimental group

Description:

Participants received 4 capsules of 100 milligrams (mg) of amcenestrant once daily (QD) from Day 1 to Day 14.

Treatment:

Drug: Amcenestrant (SAR439859)

Amcenestrant 200 mg

Experimental group

Description:

Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.

Treatment:

Drug: Amcenestrant (SAR439859)

Letrozole 2.5 mg

Active Comparator group

Description:

Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.

Treatment:

Drug: Letrozole