Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer
- Conditions
- Breast Cancer Metastatic
- Interventions
- Registration Number
- NCT04059484
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 367
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Amcenestrant Amcenestrant Daily amcenestrant dose administered orally under fed or fast condition Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator Fulvestrant 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) Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator Anastrozole 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) Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator Letrozole 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) Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator Tamoxifen 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) Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator Exemestane 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)
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) 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) PFS is defined as the time in months interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by independent central review (ICR) or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks) OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.
Percentage of Participants With Disease Control 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) Disease control is defined as percentage of participants having a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Percentage of Participants With Clinical Benefit 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) Clinical Benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Duration of Response (DOR) 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) DOR is defined as time (in months) from first documented evidence of CR or PR until progressive disease (PD) determined by ICR as per RECIST 1.1 or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Progression Free Survival (PFS) According to Estrogen Receptor 1 Gene (ESR1) Mutation Status 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) PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex droplet digital polymerase chain reaction (ddPCR), including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method.
Pharmacokinetics: Plasma Concentrations of Amcenestrant 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 Amcenestrant plasma concentrations at specified time points are reported.
Percentage of Participants With Objective Response 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) Objective response is defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by ICR. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Within-Participant Steady State Ctrough of Amcenestrant Predose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1 Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of predose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 ) was derived and reported in this outcome measure.
Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks]) EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy \& assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, \& Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional \& GHS/QoL = higher level of functioning, \& higher score for symptoms scales = higher symptom burden. Least Square (LS) mean and Standard Error (SE) are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome 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 Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks]) EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome 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 Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks]) EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) \& VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort \& anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, \& extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state \& lower score indicate worse health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported in this outcome 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 Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks]) QLQ-BR23: disease-specific Health-related QOL assesses impact of breast cancer \& side effects of treatment. EORTC-QLQ-BR23 contains 23 items: multi-item scales \& single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) \& 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, \& upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle \[Cycle 1 up to Cycle 30\]) was reported.
Trial Locations
- Locations (109)
Investigational Site Number : 8040001
🇺🇦Kryvyi Rih, Ukraine
Investigational Site Number : 3000004
🇬🇷Thessaloniki, Greece
Hospital de Clinicas de Porto Alegre - HCPA Site Number : 0760001
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Investigational Site Number : 1560008
🇨🇳Linyi, China
Investigational Site Number : 1560023
🇨🇳Hangzhou, China
Investigational Site Number : 1560005
🇨🇳Harbin, China
Investigational Site Number : 1560018
🇨🇳Hefei, China
Investigational Site Number : 1560026
🇨🇳Jinan, China
Investigational Site Number : 1560001
🇨🇳Beijing, China
Investigational Site Number : 0320007
🇦🇷Capital Federal, Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷Caba, Buenos Aires, Argentina
Comprehensive Blood and Cancer Center Site Number : 8400018
🇺🇸Bakersfield, California, United States
Gabrail Cancer Center Site Number : 8400006
🇺🇸Canton, Ohio, United States
Northwest Medical Specialties Site Number : 8400038
🇺🇸Tacoma, Washington, United States
UCLA Hematology Oncology Parkside Site Number : 8400024
🇺🇸Santa Monica, California, United States
Hackensack University Medical Center Site Number : 8400025
🇺🇸Hackensack, New Jersey, United States
The University of Kansas Clinical Research Center Site Number : 8400027
🇺🇸Fairway, Kansas, United States
Investigational Site Number : 0320005
🇦🇷Rosario, Santa Fe, Argentina
University of Wisconsin Site Number : 8400016
🇺🇸Madison, Wisconsin, United States
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320002
🇦🇷Salta, Argentina
Investigational Site Number : 1560015
🇨🇳Changchun, China
Investigational Site Number : 0360002
🇦🇺Woolloongabba, Queensland, Australia
Investigational Site Number : 0560002
🇧🇪Charleroi, Belgium
Investigational Site Number : 0560001
🇧🇪Leuven, Belgium
Investigational Site Number : 1240003
🇨🇦London, Ontario, Canada
Investigational Site Number : 1560025
🇨🇳Chengdu, China
Investigational Site Number : 1240006
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 3000001
🇬🇷Heraklion, Greece
Investigational Site Number : 3800001
🇮🇹Candiolo, Torino, Italy
Investigational Site Number : 3920001
🇯🇵Kashiwa-shi, Chiba, Japan
Investigational Site Number : 1560003
🇨🇳Kunming, China
Investigational Site Number : 1560021
🇨🇳Urumqi, China
Investigational Site Number : 3800002
🇮🇹Milano, Italy
Investigational Site Number : 4280002
🇱🇻Riga, Latvia
Investigational Site Number : 3920003
🇯🇵Osaka-shi, Osaka, Japan
Investigational Site Number : 3920006
🇯🇵Yokohama-shi, Kanagawa, Japan
Investigational Site Number : 4100003
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4840006
🇲🇽Veracruz, Mexico
Investigational Site Number : 4100004
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 3920005
🇯🇵Kitaadachi-gun, Saitama, Japan
Investigational Site Number : 6160003
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number : 6430003
🇷🇺Moscow, Russian Federation
Investigational Site Number : 7240001
🇪🇸Hospitalet de Llobregat, Barcelona [Barcelona], Spain
Investigational Site Number : 8040004
🇺🇦Odesa, Ukraine
Investigational Site Number : 7920004
🇹🇷Ankara, Turkey
Alabama Oncology Site Number : 8400008
🇺🇸Birmingham, Alabama, United States
Investigational Site Number : 7240008
🇪🇸Málaga, Spain
University Of Vermont Site Number : 8400026
🇺🇸Burlington, Vermont, United States
Dana Farber Cancer Institute Site Number : 8400015
🇺🇸Boston, Massachusetts, United States
The Center For Cancer And Blood Disorders Site Number : 8400022
🇺🇸Fort Worth, Texas, United States
Investigational Site Number : 0320006
🇦🇷Buenos Aires, Argentina
Hospital Araujo Jorge Site Number : 0760005
🇧🇷Goiania, Goiás, Brazil
Investigational Site Number : 1240004
🇨🇦Calgary, Alberta, Canada
Investigational Site Number : 0560003
🇧🇪Namur, Belgium
Hospital de Base Sao Jose do Rio Preto Site Number : 0760003
🇧🇷Sao Jose do Rio Preto, São Paulo, Brazil
Nucleo de Pesquisa Clinica e Ensino da Rede Sao Camilo Site Number : 0760006
🇧🇷Sao Paulo, São Paulo, Brazil
Investigational Site Number : 1560024
🇨🇳Chongqing, China
Investigational Site Number : 1560014
🇨🇳Changsha, China
Investigational Site Number : 1560002
🇨🇳Hangzhou, China
Investigational Site Number : 1560010
🇨🇳Hefei, China
Investigational Site Number : 1560016
🇨🇳Wuhan, China
Investigational Site Number : 1560011
🇨🇳Nanjing, China
Investigational Site Number : 1560013
🇨🇳Tianjin, China
Investigational Site Number : 1560031
🇨🇳Xuzhou, China
Investigational Site Number : 3000002
🇬🇷Larisa, Greece
Investigational Site Number : 2030002
🇨🇿Brno, Czechia
Investigational Site Number : 2500008
🇫🇷ANGERS Cedex 02, France
Investigational Site Number : 2030003
🇨🇿Novy Jicin, Czechia
Investigational Site Number : 3760001
🇮🇱Petah-Tikva, Israel
Investigational Site Number : 2500007
🇫🇷Marseille, France
Investigational Site Number : 2030004
🇨🇿Praha 4, Czechia
Investigational Site Number : 2500001
🇫🇷Villejuif, France
Investigational Site Number : 3760004
🇮🇱Tel HaShomer, Israel
Investigational Site Number : 3800003
🇮🇹Prato, Italy
Investigational Site Number : 4280001
🇱🇻Riga, Latvia
Investigational Site Number : 3920002
🇯🇵Nagoya-shi, Aichi, Japan
Investigational Site Number : 3920009
🇯🇵Ota-shi, Gunma, Japan
Investigational Site Number : 4100001
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 6160001
🇵🇱Warszawa, Mazowieckie, Poland
Torre Hospital Auxilo Mutuo Site Number : 8400028
🇵🇷Ponce De Leon 735 Hato Rey, Puerto Rico
Investigational Site Number : 6430002
🇷🇺Saint -Petersburg, Russian Federation
Investigational Site Number : 6430005
🇷🇺Moscow, Russian Federation
Investigational Site Number : 7240006
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 1580002
🇨🇳Taichung, Taiwan
Investigational Site Number : 7240003
🇪🇸Barcelona, Catalunya [Cataluña], Spain
Investigational Site Number : 1580003
🇨🇳Tainan, Taiwan
Investigational Site Number : 7920002
🇹🇷Edirne, Turkey
Investigational Site Number : 1580001
🇨🇳Taipei, Taiwan
Investigational Site Number : 7920003
🇹🇷Istanbul, Turkey
Investigational Site Number : 1580004
🇨🇳Taipei, Taiwan
Investigational Site Number : 8040005
🇺🇦Uzhgorod, Ukraine
Hematology Oncology Clinic Site Number : 8400020
🇺🇸Baton Rouge, Louisiana, United States
Investigational Site Number : 2500006
🇫🇷Creteil, France
Dartmouth Hitchcock Med Center Site Number : 8400013
🇺🇸Lebanon, New Hampshire, United States
Investigational Site Number : 0320004
🇦🇷La Rioja, Argentina
Investigational Site Number : 0360003
🇦🇺South Brisbane, Queensland, Australia
Investigational Site Number : 3760002
🇮🇱Jerusalem, Israel
Investigational Site Number : 0360001
🇦🇺Nedlands, Western Australia, Australia
Investigational Site Number : 3760003
🇮🇱Tel Aviv, Israel
Investigational Site Number : 2500005
🇫🇷Paris, France
Investigational Site Number : 3920008
🇯🇵Koto-ku, Tokyo, Japan
Investigational Site Number : 4840005
🇲🇽Mexico, Mexico
Investigational Site Number : 3920004
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number : 4840002
🇲🇽Monterrey, Nuevo León, Mexico
Investigational Site Number : 1580005
🇨🇳Taipei, Taiwan
Saint Luke's Hospital Site Number : 8400032
🇺🇸Kansas City, Missouri, United States
Hospital Mae de Deus Site Number : 0760002
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil