Clinical trial NCT04059484: Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer
Official title: An Open Label Randomized Phase 2 Trial of Amcenestrant (SAR439859), Versus Endocrine Monotherapy as Per Physician's Choice in Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormonal Therapies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer Metastatic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-08-16
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
measure: Percentage of Participants With Objective Response
timeFrame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
measure: Percentage of Participants With Disease Control
timeFrame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
measure: Percentage of Participants With Clinical Benefit
timeFrame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
measure: Duration of Response (DOR)
timeFrame: From the date of first response to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
measure: Progression Free Survival (PFS) According to Estrogen Receptor 1 Gene (ESR1) Mutation Status
timeFrame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
measure: Pharmacokinetics: Plasma Concentrations of Amcenestrant
timeFrame: Cycle 1 Day 1: 1.5 hours(h), 4h post-dose, Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 1.5h, 4h, 8h post-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 6 Day 1: pre-dose
measure: Within-Participant Steady State Ctrough of Amcenestrant
timeFrame: Predose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores
timeFrame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
measure: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score
timeFrame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
measure: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value
timeFrame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores
timeFrame: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology Site Number : 8400008
state: Alabama
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center Site Number : 8400018
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology Parkside Site Number : 8400024
state: California
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center Site Number : 8400027
state: Kansas
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic Site Number : 8400020
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute Site Number : 8400015
state: Massachusetts
city: Kansas City
country: United States
facility: Saint Luke's Hospital Site Number : 8400032
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Med Center Site Number : 8400013
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center Site Number : 8400025
state: New Jersey
city: Canton
country: United States
facility: Gabrail Cancer Center Site Number : 8400006
state: Ohio
city: Fort Worth
country: United States
facility: The Center For Cancer And Blood Disorders Site Number : 8400022
state: Texas
city: Burlington
country: United States
facility: University Of Vermont Site Number : 8400026
state: Vermont
city: Tacoma
country: United States
facility: Northwest Medical Specialties Site Number : 8400038
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Site Number : 8400016
state: Wisconsin
city: Caba
country: Argentina
facility: Investigational Site Number : 0320008
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Investigational Site Number : 0320007
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320005
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320006
city: La Rioja
country: Argentina
facility: Investigational Site Number : 0320004
city: Salta
country: Argentina
facility: Investigational Site Number : 0320002
city: South Brisbane
country: Australia
facility: Investigational Site Number : 0360003
state: Queensland
city: Woolloongabba
country: Australia
facility: Investigational Site Number : 0360002
state: Queensland
city: Nedlands
country: Australia
facility: Investigational Site Number : 0360001
state: Western Australia
city: Charleroi
country: Belgium
facility: Investigational Site Number : 0560002
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Namur
country: Belgium
facility: Investigational Site Number : 0560003
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge Site Number : 0760005
state: Goiás
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre - HCPA Site Number : 0760001
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus Site Number : 0760002
state: Rio Grande Do Sul
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base Sao Jose do Rio Preto Site Number : 0760003
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Nucleo de Pesquisa Clinica e Ensino da Rede Sao Camilo Site Number : 0760006
state: São Paulo
city: Calgary
country: Canada
facility: Investigational Site Number : 1240004
state: Alberta
city: London
country: Canada
facility: Investigational Site Number : 1240003
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240006
state: Quebec
city: Beijing
country: China
facility: Investigational Site Number : 1560001
city: Changchun
country: China
facility: Investigational Site Number : 1560015
city: Changsha
country: China
facility: Investigational Site Number : 1560014
city: Chengdu
country: China
facility: Investigational Site Number : 1560025
city: Chongqing
country: China
facility: Investigational Site Number : 1560024
city: Hangzhou
country: China
facility: Investigational Site Number : 1560023
city: Hangzhou
country: China
facility: Investigational Site Number : 1560002
city: Harbin
country: China
facility: Investigational Site Number : 1560005
city: Hefei
country: China
facility: Investigational Site Number : 1560010
city: Hefei
country: China
facility: Investigational Site Number : 1560018
city: Jinan
country: China
facility: Investigational Site Number : 1560026
city: Kunming
country: China
facility: Investigational Site Number : 1560003
city: Linyi
country: China
facility: Investigational Site Number : 1560008
city: Nanjing
country: China
facility: Investigational Site Number : 1560011
city: Tianjin
country: China
facility: Investigational Site Number : 1560013
city: Urumqi
country: China
facility: Investigational Site Number : 1560021
city: Wuhan
country: China
facility: Investigational Site Number : 1560016
city: Xuzhou
country: China
facility: Investigational Site Number : 1560031
city: Brno
country: Czechia
facility: Investigational Site Number : 2030002
city: Novy Jicin
country: Czechia
facility: Investigational Site Number : 2030003
city: Praha 4
country: Czechia
facility: Investigational Site Number : 2030004
city: ANGERS Cedex 02
country: France
facility: Investigational Site Number : 2500008
city: Creteil
country: France
facility: Investigational Site Number : 2500006
city: Marseille
country: France
facility: Investigational Site Number : 2500007
city: Paris
country: France
facility: Investigational Site Number : 2500005
city: Villejuif
country: France
facility: Investigational Site Number : 2500001
city: Heraklion
country: Greece
facility: Investigational Site Number : 3000001
city: Larisa
country: Greece
facility: Investigational Site Number : 3000002
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000004
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760002
city: Petah-Tikva
country: Israel
facility: Investigational Site Number : 3760001
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 3760003
city: Tel HaShomer
country: Israel
facility: Investigational Site Number : 3760004
city: Candiolo
country: Italy
facility: Investigational Site Number : 3800001
state: Torino
city: Milano
country: Italy
facility: Investigational Site Number : 3800002
city: Prato
country: Italy
facility: Investigational Site Number : 3800003
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Aichi
city: Kashiwa-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Chiba
city: Ota-shi
country: Japan
facility: Investigational Site Number : 3920009
state: Gunma
city: Yokohama-shi
country: Japan
facility: Investigational Site Number : 3920006
state: Kanagawa
city: Osaka-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Investigational Site Number : 3920005
state: Saitama
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920004
state: Tokyo
city: Koto-ku
country: Japan
facility: Investigational Site Number : 3920008
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Riga
country: Latvia
facility: Investigational Site Number : 4280002
city: Riga
country: Latvia
facility: Investigational Site Number : 4280001
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840002
state: Nuevo León
city: Mexico
country: Mexico
facility: Investigational Site Number : 4840005
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840006
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160003
state: Wielkopolskie
city: Ponce De Leon 735 Hato Rey
country: Puerto Rico
facility: Torre Hospital Auxilo Mutuo Site Number : 8400028
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430003
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430005
city: Saint -Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240006
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Catalunya [Cataluña]
city: Málaga
country: Spain
facility: Investigational Site Number : 7240008
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580002
city: Tainan
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580005
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580004
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920004
city: Edirne
country: Turkey
facility: Investigational Site Number : 7920002
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920003
city: Kryvyi Rih
country: Ukraine
facility: Investigational Site Number : 8040001
city: Odesa
country: Ukraine
facility: Investigational Site Number : 8040004
city: Uzhgorod
country: Ukraine
facility: Investigational Site Number : 8040005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.