AMEERA-3: Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer

Sponsor

Sanofi (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04059484

Collaborator

(none)

367

Enrollment

122

Locations

Arms

47.2

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To determine whether amcenestrant per os improves progression free survival (PFS) when compared with a 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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Metastatic	Drug: Amcenestrant Drug: Fulvestrant Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Tamoxifen	Phase 2

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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

367 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 22, 2019

Actual Primary Completion Date :

Feb 15, 2022

Anticipated Study Completion Date :

Sep 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Amcenestrant Daily amcenestrant dose administered orally under fed or fast condition	Drug: Amcenestrant Pharmaceutical form: Capsule Route of administration: Oral
Active Comparator: 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)	Drug: Fulvestrant Pharmaceutical form: Solution for injection Route of administration: Intramuscular Other Names: Faslodex® Drug: Anastrozole Pharmaceutical form:Tablets or capsules Route of administration: Oral Other Names: Arimidex®/Anastrozole Generics Drug: Letrozole Pharmaceutical form: Tablets or capsules Route of administration: Oral Other Names: Femara®/Letrozole Generics Drug: Exemestane Pharmaceutical form: Tablets or capsules Route of administration: Oral Other Names: Aromasin®/Exemestane Generics Drug: Tamoxifen Pharmaceutical form: Tablets or capsules Route of administration: Oral Other Names: Nolvadex®/Tamoxifen Generics

Arm

Intervention/Treatment

Experimental: Amcenestrant

Daily amcenestrant dose administered orally under fed or fast condition

Drug: Amcenestrant

Pharmaceutical form: Capsule Route of administration: Oral

Active Comparator: 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)

Drug: Fulvestrant

Pharmaceutical form: Solution for injection Route of administration: Intramuscular

Other Names:

Faslodex®

Drug: Anastrozole

Pharmaceutical form:Tablets or capsules Route of administration: Oral

Other Names:

Arimidex®/Anastrozole Generics

Drug: Letrozole

Pharmaceutical form: Tablets or capsules Route of administration: Oral

Other Names:

Femara®/Letrozole Generics

Drug: Exemestane

Pharmaceutical form: Tablets or capsules Route of administration: Oral

Other Names:

Aromasin®/Exemestane Generics

Drug: Tamoxifen

Pharmaceutical form: Tablets or capsules Route of administration: Oral

Other Names:

Nolvadex®/Tamoxifen Generics

Outcome Measures

Primary Outcome Measures

Progression free survival (PFS) [Up to 18 months after the first randomized participant]
PFS is defined as the time interval from the date of randomization to the date of documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever comes first.

Secondary Outcome Measures

Overall Survival (OS) [Up to 64 months after the first randomized participant]
OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
Objective Response Rate (ORR) [Up to 18 months after the first randomized participant]
ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), as best overall response (BOR) determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
Disease Control Rate (DCR) [Up to 18 months after the first randomized participant]
DCR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
Clinical Benefit Rate (CBR) [Up to 18 months after the first randomized participant]
CBR is defined as the proportion of participants who have a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
Duration of Response (DOR) [Up to 18 months after the first randomized participant]
DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by objective radiographic disease assessment per RECIST 1.1 or death from any cause, whichever occurs first.
PFS according to (ESR1) mutation status [Up to 18 months after the first randomized participant]
PFS as per the estrogen receptor 1 (ESR1) mutation status determined at study entry.
Assessments of the pharmacokinetic (PK) parameter of amcenestrant as single agent: plasma concentrations [Day 1 and Day 15 of Cycle 1 and Day 1 of cycles 3, 4 and 6 (each cycle is 28 days)]
Amcenestrant plasma concentrations.
Patient Reported Outcome (PRO) - health-related quality of life and health status using the European Quality of Life-5 Dimensions (EQ-5D) [Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days)]
EQ-5D is a standardized measure of health status.
Patient Reported Outcome (PRO) - the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC-QLQ-C30) [Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days)]
The EORTC-QLQ-C30 is composed of both multi item scales and single item measures. These include 5 functional scales, 3 symptom scales, a Global Health Status (GHS)/quality of life scale, and 6 single items.
Patient Reported Outcome (PRO) - EORTC-QLQ breast cancer (EORTC-QLQ-BR23) [Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days)]
The EORTC-QLQ-BR23 contains 23 items: 8 assessing function and 15 items assessing symptoms of disease or treatment.
Overall safety profile - Treatment-Emergent Adverse events [Evaluated continuously throughout study from the date of enrollment, up to 30 days after last study treatment administration]
Number of participants with treatment-emergent adverse events (TEAEs).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
ER positive status.
HER2 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 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 >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 UGT less than 2 weeks before randomization.
Treatment with strong CYP3A 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number :8400008	Birmingham	Alabama	United States	35205
2	Investigational Site Number :8400018	Bakersfield	California	United States	93309
3	Investigational Site Number :8400024	Santa Monica	California	United States	90404
4	Investigational Site Number :8400034	Iowa City	Iowa	United States	52242
5	Investigational Site Number :8400027	Fairway	Kansas	United States	66205
6	Investigational Site Number :8400020	Baton Rouge	Louisiana	United States	70808
7	Investigational Site Number :8400015	Boston	Massachusetts	United States	02115
8	Investigational Site Number :8400032	Kansas City	Missouri	United States	64111
9	Investigational Site Number :8400013	Lebanon	New Hampshire	United States	03756
10	Investigational Site Number :8400025	Hackensack	New Jersey	United States	07601
11	Investigational Site Number :8400009	Jamaica	New York	United States	11432
12	Investigational Site Number :8400030	Pinehurst	North Carolina	United States	28374
13	Investigational Site Number :8400006	Canton	Ohio	United States	44718
14	Investigational Site Number :8400014	Tulsa	Oklahoma	United States	74133
15	Investigational Site Number :8400022	Fort Worth	Texas	United States	76104
16	Investigational Site Number :8400026	Burlington	Vermont	United States	05401
17	Investigational Site Number :8400038	Tacoma	Washington	United States	98405
18	Investigational Site Number :8400016	Madison	Wisconsin	United States	53792
19	Investigational Site Number :0320007	Buenos Aires		Argentina	1012
20	Investigational Site Number :0320001	Buenos Aires		Argentina	1426ANZ
21	Investigational Site Number :0320008	Buenos Aires		Argentina	C1019ABS
22	Investigational Site Number :0320006	Buenos Aires		Argentina	C1125ABD
23	Investigational Site Number :0320004	La Rioja		Argentina	5300
24	Investigational Site Number :0320005	Rosario		Argentina	2000
25	Investigational Site Number :0320002	Salta		Argentina	4400
26	Investigational Site Number :0360003	South Brisbane	Queensland	Australia	4101
27	Investigational Site Number :0360001	Nedlands	Western Australia	Australia	6009
28	Investigational Site Number :0360002	Woolloongabba		Australia	4102
29	Investigational Site Number :0560002	Charleroi		Belgium	B-6000
30	Investigational Site Number :0560001	Leuven		Belgium	3000
31	Investigational Site Number :0560003	Namur		Belgium	5000
32	Investigational Site Number :0760003	Sao Jose do Rio Preto	São Paulo	Brazil	15090-000
33	Investigational Site Number :0760005	Goiania		Brazil	74605-070
34	Investigational Site Number :0760001	Porto Alegre		Brazil	90035 003
35	Investigational Site Number :0760002	Porto Alegre		Brazil	90110-270
36	Investigational Site Number :0760006	Sao Paulo		Brazil	04014-002
37	Investigational Site Number :1240004	Calgary	Alberta	Canada	T2N 4N2
38	Investigational Site Number :1240003	London	Ontario	Canada	N6A 5W9
39	Investigational Site Number :1240006	Montreal	Quebec	Canada	H3T 1E2
40	Investigational Site Number :1560001	Beijing		China	100142
41	Investigational Site Number :1560019	Changchun		China	130012
42	Investigational Site Number :1560015	Changchun		China	130021
43	Investigational Site Number :1560014	Changsha		China	410005
44	Investigational Site Number :1560025	Chengdu		China	610041
45	Investigational Site Number :1560024	Chongqing		China	400030
46	Investigational Site Number :1560030	Dalian		China	116011
47	Investigational Site Number :1560023	Hangzhou		China	310016
48	Investigational Site Number :1560002	Hangzhou		China	310022
49	Investigational Site Number :1560005	Harbin		China	150081
50	Investigational Site Number :1560010	Hefei		China	230001
51	Investigational Site Number :1560018	Hefei		China	230022
52	Investigational Site Number :1560026	Jinan		China	250013
53	Investigational Site Number :1560003	Kunming		China	650118
54	Investigational Site Number :1560008	Linyi		China	276000
55	Investigational Site Number :1560011	Nanjing		China	210029
56	Investigational Site Number :1560027	Shanghai		China	200032
57	Investigational Site Number :1560004	Shijiazhuang		China
58	Investigational Site Number :1560013	Tianjin		China	300060
59	Investigational Site Number :1560021	Urumqi		China	830000
60	Investigational Site Number :1560016	Wuhan		China	430079
61	Investigational Site Number :1560033	Xiamen		China	361003
62	Investigational Site Number :1560032	Xuzhou		China	221002
63	Investigational Site Number :1560031	Xuzhou		China
64	Investigational Site Number :2030002	Brno		Czechia	65653
65	Investigational Site Number :2030003	Novy Jicin		Czechia	741 01
66	Investigational Site Number :2030004	Praha 4		Czechia	14059
67	Investigational Site Number :2500008	Angers		France	49055
68	Investigational Site Number :2500006	Creteil		France	94000
69	Investigational Site Number :2500007	Marseille		France	13009
70	Investigational Site Number :2500005	Paris		France	75010
71	Investigational Site Number :2500002	Saint-Herblain		France	44805
72	Investigational Site Number :2500001	Villejuif		France	94800
73	Investigational Site Number :3000003	Athens		Greece	14564
74	Investigational Site Number :3000001	Heraklion		Greece	71110
75	Investigational Site Number :3000002	Larissa		Greece	41110
76	Investigational Site Number :3000004	Thessaloniki		Greece	54645
77	Investigational Site Number :3760002	Jerusalem		Israel	91031
78	Investigational Site Number :3760001	Petah-Tikva		Israel	49100
79	Investigational Site Number :3760003	Tel Aviv		Israel	64239
80	Investigational Site Number :3760004	Tel HaShomer		Israel	52621
81	Investigational Site Number :3800001	Candiolo	Torino	Italy	10060
82	Investigational Site Number :3800002	Milano		Italy	20141
83	Investigational Site Number :3800003	Prato		Italy	59100
84	Investigational Site Number :3920002	Nagoya-shi	Aichi	Japan	464-8681
85	Investigational Site Number :3920001	Kashiwa-shi	Chiba	Japan	277-8577
86	Investigational Site Number :3920009	Ota-shi	Gunma	Japan	373-8550
87	Investigational Site Number :3920006	Yokohama-shi	Kanagawa	Japan	241-8515
88	Investigational Site Number :3920005	Kitaadachi-gun	Saitama	Japan	362-0806
89	Investigational Site Number :3920004	Chuo-ku	Tokyo	Japan	104-0045
90	Investigational Site Number :3920008	Koto-ku	Tokyo	Japan	135-8550
91	Investigational Site Number :3920003	Osaka-shi		Japan	540-0006
92	Investigational Site Number :4100001	Seoul		Korea, Republic of	03080
93	Investigational Site Number :4100004	Seoul		Korea, Republic of	03722
94	Investigational Site Number :4100003	Seoul		Korea, Republic of	05505
95	Investigational Site Number :4100002	Seoul		Korea, Republic of	06351
96	Investigational Site Number :4280002	Riga		Latvia	LV-1002
97	Investigational Site Number :4280001	Riga		Latvia	LV-1038
98	Investigational Site Number :4840005	Mexico		Mexico	03100
99	Investigational Site Number :4840002	Monterrey		Mexico	64460
100	Investigational Site Number :4840006	Veracruz		Mexico	91910
101	Investigational Site Number :6160003	Poznan		Poland	61-866
102	Investigational Site Number :6160001	Warszawa		Poland	02-781
103	Investigational Site Number :8400028	Ponce De Leon		Puerto Rico	00917
104	Investigational Site Number :6430003	Moscow		Russian Federation	115478
105	Investigational Site Number :6430005	Moscow		Russian Federation	129090
106	Investigational Site Number :6430002	Saint -Petersburg		Russian Federation	197758
107	Investigational Site Number :7240006	Barcelona		Spain	08035
108	Investigational Site Number :7240003	Barcelona		Spain	08036
109	Investigational Site Number :7240001	Hospitalet de Llobregat		Spain	08908
110	Investigational Site Number :7240008	Málaga		Spain	29010
111	Investigational Site Number :1580002	Taichung		Taiwan	40447
112	Investigational Site Number :1580003	Tainan		Taiwan	704
113	Investigational Site Number :1580001	Taipei		Taiwan	10018
114	Investigational Site Number :1580005	Taipei		Taiwan	104
115	Investigational Site Number :1580004	Taipei		Taiwan	114
116	Investigational Site Number :7920004	Ankara		Turkey	06200
117	Investigational Site Number :7920002	Edirne		Turkey	22030
118	Investigational Site Number :7920001	Istanbul		Turkey	34303
119	Investigational Site Number :7920003	Istanbul		Turkey	34722
120	Investigational Site Number :8040001	Kryvyi Rih		Ukraine	50048
121	Investigational Site Number :8040004	Odesa		Ukraine	65025
122	Investigational Site Number :8040005	Uzhgorod		Ukraine	88000