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

NCT ID: NCT04191382

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-04
• Study Completion Date: 2021-05-28

Brief Summary

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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Amcenestrant 400 mg

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

Group Type: EXPERIMENTAL

Amcenestrant (SAR439859)

Intervention Type: DRUG

Pharmaceutical form: Capsules, Route of administration: Oral

Amcenestrant 200 mg

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

Group Type: EXPERIMENTAL

Amcenestrant (SAR439859)

Intervention Type: DRUG

Pharmaceutical form: Capsules, Route of administration: Oral

Letrozole 2.5 mg

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

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

Pharmaceutical form: Tablets, Route of administration: Oral

Interventions

Amcenestrant (SAR439859)

Pharmaceutical form: Capsules, Route of administration: Oral

Intervention Type: DRUG

Letrozole

Pharmaceutical form: Tablets, Route of administration: Oral

Intervention Type: DRUG

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 (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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400014

Tucson, Arizona, United States

Investigational Site Number 8400010

Los Angeles, California, United States

Investigational Site Number 8400018

Fort Wayne, Indiana, United States

Investigational Site Number 8400005

Lincoln, Nebraska, United States

Investigational Site Number 8400016

Winston-Salem, North Carolina, United States

Investigational Site Number 8400012

Tacoma, Washington, United States

Investigational Site Number 0560001

Leuven, , Belgium

Investigational Site Number 0560002

Namur, , Belgium

Investigational Site Number 2500001

Nantes, , France

Investigational Site Number 2500004

Paris, , France

Investigational Site Number 2500002

Saint-Cloud, , France

Investigational Site Number 2500003

Toulouse, , France

Investigational Site Number 3800004

Meldola, , Italy

Investigational Site Number 3800002

Milan, , Italy

Investigational Site Number 3800001

Milan, , Italy

Investigational Site Number 3920002

Osaka, , Japan

Investigational Site Number 3920003

Sapporo, , Japan

Investigational Site Number 3920001

Yokohama, , Japan

Investigational Site Number 8400007

Hato Rey, , Puerto Rico

Investigational Site Number 6430006

Moscow, , Russia

Investigational Site Number 6430004

Moscow, , Russia

Investigational Site Number 6430003

Saint Petersburg, , Russia

Investigational Site Number 6430007

Saint Petersburg, , Russia

Investigational Site Number 6430002

Saint Petersburg, , Russia

Investigational Site Number 7240005

Barcelona, , Spain

Investigational Site Number 7240003

Córdoba, , Spain

Investigational Site Number 7240001

Madrid, , Spain

Investigational Site Number 7240002

Valencia, , Spain

Investigational Site Number 8040004

Kharkiv, , Ukraine

Investigational Site Number 8040001

Uzhhorod, , Ukraine

Investigational Site Number 8040002

Vinnytsia, , Ukraine

Investigational Site Number 8040005

Zaporizhzhya, , Ukraine

Countries

United States; Belgium; France; Italy; Japan; Puerto Rico; Russia; Spain; Ukraine

References

Campone M, Bidard FC, Neven P, Wang L, Ling B, Dong Y, Paux G, Herold C, De Giorgi U. AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer. Breast Cancer Res. 2023 Nov 10;25(1):141. doi: 10.1186/s13058-023-01740-2.

Reference Type: DERIVED

PMID: 37950338 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25188&tenant=MT_SNY_9011

ACT16106 Plain Language Results Summary

Other Identifiers

2019-002015-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1228-9473

Identifier Type: OTHER

Identifier Source: secondary_id

ACT16106

Identifier Type: -

Identifier Source: org_study_id