Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer

NCT ID: NCT04059484

Last Updated: 2025-01-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 367 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-22
• Study Completion Date: 2025-01-02

Brief Summary

Primary Objective:

To determine whether amcenestrant per overall survival (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 overall survival in the 2 treatment arms
• To assess 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 pharmacokinetics of amcenestrant as single agent
• To evaluate health-related quality of life in the 2 treatment arms
• To compare 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 to stop treatment, or Investigator decision, whichever occurs first.

An extension of recruitment for Chinese participants is planned in this study: After completion of randomization in the global part of the study, randomization will continue in China until approximately 90 Chinese participants are randomized.

Conditions

Breast Cancer Metastatic

Study Design

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

Study Groups

Amcenestrant

Daily amcenestrant dose administered orally under fed or fast condition

Group Type: EXPERIMENTAL

Amcenestrant

Intervention Type: DRUG

Pharmaceutical form: Capsule

Route of administration: Oral

Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator

Control treatment of the choice of the physician depending on each participant's medical condition and in accordance with the approved label may include 1 of the following treatments used as monotherapy.

Fulvestrant

Aromatase inhibitors (anastrozole, letrozole, exemestane)

Selective estrogen receptor modulator (Tamoxifen)

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Intramuscular

Anastrozole

Intervention Type: DRUG

Pharmaceutical form:Tablets or capsules

Route of administration: Oral

Letrozole

Intervention Type: DRUG

Pharmaceutical form: Tablets or capsules

Route of administration: Oral

Exemestane

Intervention Type: DRUG

Pharmaceutical form: Tablets or capsules

Route of administration: Oral

Tamoxifen

Intervention Type: DRUG

Pharmaceutical form: Tablets or capsules

Route of administration: Oral

Interventions

Amcenestrant

Pharmaceutical form: Capsule

Route of administration: Oral

Intervention Type: DRUG

Fulvestrant

Pharmaceutical form: Solution for injection

Route of administration: Intramuscular

Intervention Type: DRUG

Anastrozole

Pharmaceutical form:Tablets or capsules

Route of administration: Oral

Intervention Type: DRUG

Letrozole

Pharmaceutical form: Tablets or capsules

Route of administration: Oral

Intervention Type: DRUG

Exemestane

Pharmaceutical form: Tablets or capsules

Route of administration: Oral

Intervention Type: DRUG

Tamoxifen

Pharmaceutical form: Tablets or capsules

Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

Faslodex®; Arimidex®/Anastrozole Generics; Femara®/Letrozole Generics; Aromasin®/Exemestane Generics; Nolvadex®/Tamoxifen Generics

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.
• Estrogen receptor(ER) positive status.
• Human epidermal growth factor receptor 2 negative status.
• Participants must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease.
• In the main study, a prior treatment with a Cyclin-dependent kinase 4 and 6(CDK 4/6) inhibitor is mandatory if this treatment is approved and can be reimbursed for this participant. The percentage of participants without previous CDK 4/6 inhibitor will be capped to 20%. In the Chinese extension cohort, previous treatment with a CDK 4/6 inhibitor will not be mandatory, and there will be no limitation to the number of participants naïve to CDK4/6 inhibitor.
• Participants must present a secondary endocrine resistance to endocrine therapy defined as: progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months after completing adjuvant endocrine therapy.
• Male or Female.

Exclusion Criteria

• Eastern Cooperative Oncology Group performance status =>2.
• Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant. 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 greater than 3 years are allowed.
• Severe uncontrolled systemic disease at screening .
• Participants with known brain metastases that are untreated, symptomatic or require therapy to control symptoms.
• Prior treatment with mammalian target of rapamycin inhibitors or any other selective estrogen receptor degrader(SERD) compound, except fulvestrant if stopped for at least 3 months before randomization.
• Treatment with drugs that have the potential to inhibit Uridine'5 Diphospho-Glucuronosyl Transferase(UGT) less than 2 weeks before randomization.
• Treatment with strong Cytochrome P450 (CYP)3A inducers within 2 weeks before randomization.
• Ongoing treatment with drugs that are sensitive substrate of organic anion transporting polypeptide 1B1/B3(OATP1B1/B3) (asunaprevir, atorvastatin, bosentan, danoprevir, fexofenadine, glyburide, nateglinide, pitavastatin, pravastatin, replaglinide, rosuvastatin, and simvastatin acid).
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• 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

Alabama Oncology Site Number : 8400008

Birmingham, Alabama, United States

Comprehensive Blood and Cancer Center Site Number : 8400018

Bakersfield, California, United States

UCLA Hematology Oncology Parkside Site Number : 8400024

Santa Monica, California, United States

The University of Kansas Clinical Research Center Site Number : 8400027

Fairway, Kansas, United States

Hematology Oncology Clinic Site Number : 8400020

Baton Rouge, Louisiana, United States

Dana Farber Cancer Institute Site Number : 8400015

Boston, Massachusetts, United States

Saint Luke's Hospital Site Number : 8400032

Kansas City, Missouri, United States

Dartmouth Hitchcock Med Center Site Number : 8400013

Lebanon, New Hampshire, United States

Hackensack University Medical Center Site Number : 8400025

Hackensack, New Jersey, United States

Gabrail Cancer Center Site Number : 8400006

Canton, Ohio, United States

The Center For Cancer And Blood Disorders Site Number : 8400022

Fort Worth, Texas, United States

University Of Vermont Site Number : 8400026

Burlington, Vermont, United States

Northwest Medical Specialties Site Number : 8400038

Tacoma, Washington, United States

University of Wisconsin Site Number : 8400016

Madison, Wisconsin, United States

Investigational Site Number : 0320008

CABA, Buenos Aires, Argentina

Investigational Site Number : 0320007

Capital Federal, Buenos Aires, Argentina

Investigational Site Number : 0320005

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320001

Buenos Aires, , Argentina

Investigational Site Number : 0320006

Buenos Aires, , Argentina

Investigational Site Number : 0320004

La Rioja, , Argentina

Investigational Site Number : 0320002

Salta, , Argentina

Investigational Site Number : 0360003

South Brisbane, Queensland, Australia

Investigational Site Number : 0360002

Woolloongabba, Queensland, Australia

Investigational Site Number : 0360001

Nedlands, Western Australia, Australia

Investigational Site Number : 0560002

Charleroi, , Belgium

Investigational Site Number : 0560001

Leuven, , Belgium

Investigational Site Number : 0560003

Namur, , Belgium

Hospital Araujo Jorge Site Number : 0760005

Goiânia, Goiás, Brazil

Hospital de Clinicas de Porto Alegre - HCPA Site Number : 0760001

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Mae de Deus Site Number : 0760002

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Base Sao Jose do Rio Preto Site Number : 0760003

São José do Rio Preto, São Paulo, Brazil

Nucleo de Pesquisa Clinica e Ensino da Rede Sao Camilo Site Number : 0760006

São Paulo, São Paulo, Brazil

Investigational Site Number : 1240004

Calgary, Alberta, Canada

Investigational Site Number : 1240003

London, Ontario, Canada

Investigational Site Number : 1240006

Montreal, Quebec, Canada

Investigational Site Number : 1560001

Beijing, , China

Investigational Site Number : 1560015

Changchun, , China

Investigational Site Number : 1560014

Changsha, , China

Investigational Site Number : 1560025

Chengdu, , China

Investigational Site Number : 1560024

Chongqing, , China

Investigational Site Number : 1560023

Hangzhou, , China

Investigational Site Number : 1560002

Hangzhou, , China

Investigational Site Number : 1560005

Harbin, , China

Investigational Site Number : 1560010

Hefei, , China

Investigational Site Number : 1560018

Hefei, , China

Investigational Site Number : 1560026

Jinan, , China

Investigational Site Number : 1560003

Kunming, , China

Investigational Site Number : 1560008

Linyi, , China

Investigational Site Number : 1560011

Nanjing, , China

Investigational Site Number : 1560013

Tianjin, , China

Investigational Site Number : 1560021

Ürümqi, , China

Investigational Site Number : 1560016

Wuhan, , China

Investigational Site Number : 1560031

Xuzhou, , China

Investigational Site Number : 2030002

Brno, , Czechia

Investigational Site Number : 2030003

Nový Jičín, , Czechia

Investigational Site Number : 2030004

Prague, , Czechia

Investigational Site Number : 2500008

Angers, , France

Investigational Site Number : 2500006

Créteil, , France

Investigational Site Number : 2500007

Marseille, , France

Investigational Site Number : 2500005

Paris, , France

Investigational Site Number : 2500001

Villejuif, , France

Investigational Site Number : 3000001

Heraklion, , Greece

Investigational Site Number : 3000002

Larissa, , Greece

Investigational Site Number : 3000004

Thessaloniki, , Greece

Investigational Site Number : 3760002

Jerusalem, , Israel

Investigational Site Number : 3760001

Petah Tikva, , Israel

Investigational Site Number : 3760003

Tel Aviv, , Israel

Investigational Site Number : 3760004

Tel Litwinsky, , Israel

Investigational Site Number : 3800001

Candiolo, Torino, Italy

Investigational Site Number : 3800002

Milan, , Italy

Investigational Site Number : 3800003

Prato, , Italy

Investigational Site Number : 3920002

Nagoya, Aichi-ken, Japan

Investigational Site Number : 3920001

Kashiwa-shi, Chiba, Japan

Investigational Site Number : 3920009

Ota-shi, Gunma, Japan

Investigational Site Number : 3920006

Yokohama, Kanagawa, Japan

Investigational Site Number : 3920003

Osaka, Osaka, Japan

Investigational Site Number : 3920005

Kitaadachi-gun, Saitama, Japan

Investigational Site Number : 3920004

Chuo-ku, Tokyo, Japan

Investigational Site Number : 3920008

Koto-ku, Tokyo, Japan

Investigational Site Number : 4280002

Riga, , Latvia

Investigational Site Number : 4280001

Riga, , Latvia

Investigational Site Number : 4840002

Monterrey, Nuevo León, Mexico

Investigational Site Number : 4840005

México, , Mexico

Investigational Site Number : 4840006

Veracruz, , Mexico

Investigational Site Number : 6160003

Poznan, Greater Poland Voivodeship, Poland

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, Poland

Torre Hospital Auxilo Mutuo Site Number : 8400028

Ponce de Leon 735 Hato Rey, Puerto Rico, Puerto Rico

Investigational Site Number : 6430003

Moscow, , Russia

Investigational Site Number : 6430005

Moscow, , Russia

Investigational Site Number : 6430002

Saint Petersburg, , Russia

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 7240006

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7240001

L'Hospitalet de Llobregat, Barcelona [Barcelona], Spain

Investigational Site Number : 7240003

Barcelona, Catalunya [Cataluña], Spain

Investigational Site Number : 7240008

Málaga, , Spain

Investigational Site Number : 1580002

Taichung, , Taiwan

Investigational Site Number : 1580003

Tainan City, , Taiwan

Investigational Site Number : 1580001

Taipei, , Taiwan

Investigational Site Number : 1580005

Taipei, , Taiwan

Investigational Site Number : 1580004

Taipei, , Taiwan

Investigational Site Number : 7920004

Ankara, , Turkey (Türkiye)

Investigational Site Number : 7920002

Edirne, , Turkey (Türkiye)

Investigational Site Number : 7920003

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 8040001

Kryvyi Rih, , Ukraine

Investigational Site Number : 8040004

Odesa, , Ukraine

Investigational Site Number : 8040005

Uzhhorod, , Ukraine

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; China; Czechia; France; Greece; Israel; Italy; Japan; Latvia; Mexico; Poland; Puerto Rico; Russia; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine

References

Tolaney SM, Chan A, Petrakova K, Delaloge S, Campone M, Iwata H, Peddi PF, Kaufman PA, De Kermadec E, Liu Q, Cohen P, Paux G, Wang L, Ternes N, Boitier E, Im SA. AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. J Clin Oncol. 2023 Aug 20;41(24):4014-4024. doi: 10.1200/JCO.22.02746. Epub 2023 Jun 22.

Reference Type: RESULT

PMID: 37348019 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1217-2774

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-004593-98

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT16105

Identifier Type: -

Identifier Source: org_study_id