July 10, 2020
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July 20, 2020
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September 22, 2022
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October 14, 2020
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June 28, 2022 (Final data collection date for primary outcome measure)
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Progression-free survival [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years) ] Progression-free survival is defined as the time 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) or death (due to any cause), whichever come first.
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Progression-free survival [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 3.5 years) ] Progression-free survival is defined as the time 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) or death (due to any cause), whichever come first.
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- Overall Survival [ Time Frame: From randomization date to date of death (up to approximately 6 years) ]
Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
- Objective Response Rate [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
Objective response rate is defined as the proportion of participants who have a CR or PR, as best overall response determined as per RECIST 1.1, from the date of randomization to the date of until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first.
- Duration of Response [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined as per RECIST 1.1 or death from any cause, whichever occurs first.
- Clinical Benefit Rate [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR, or SD for at least 24 weeks determined as per RECIST 1.1, from the date of randomization until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first
- PK parameter: Plasma concentrations [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
Plasma concentrations of Amcenestrant and palbociclib.
- Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: From Baseline up to end of study (approximately 6.5 years) ]
Incidence of participants with TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE V5
- Time to First Chemotherapy [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
Time to chemotherapy is defined as the time interval from the date of randomization to the start date of the first chemotherapy after study treatment discontinuation.
- Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
Change From Baseline between treatment comparison Using the European Quality of Life- 5-Dimension 5 Level (EQ-5D 5L).
- Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
Change From Baseline between treatment comparison in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
- Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR45) questionnaire [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR45 (Breast) Questionnaire.
- Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR23) questionnaire [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire.
- Progression-free survival on next line of therapy (PFS2) [ Time Frame: From randomization date to date of death (up to approximately 6.5 years) ]
PFS2 is defined as the time from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator or death due to any cause, whichever occurs first.
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- Overall Survival [ Time Frame: From randomization date to date of death (up to approximately 6 years) ]
Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
- Objective Response Rate [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
Objective response rate is defined as the proportion of participants who have a CR or PR, as best overall response determined as per RECIST 1.1, from the date of randomization to the date of until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first.
- Duration of Response [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined as per RECIST 1.1 or death from any cause, whichever occurs first.
- Clinical Benefit Rate [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR, or SD for at least 24 weeks determined as per RECIST 1.1, from the date of randomization until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first.
- PK parameter: Plasma concentrations [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
Plasma concentrations of SAR439859, goserelin and palbociclib
- Change From Baseline between treatment comparison Using the European Quality of Life- 5-Dimension 5 Level (EQ-5D 5L) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 3.5 years) ]
Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L).
- Change From Baseline between treatment comparison in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 3.5 years) ]
Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30).
- Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR45 (Breast) Questionnaire [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 3.5 years) ]
Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR45) questionnaire.
- Time to First Chemotherapy [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
Time to chemotherapy is defined as the time interval from the date of randomization to the start date of the first chemotherapy after study treatment discontinuation.
- Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: From Baseline up to end of study (approximately 6 years) ]
Incidence of participants with TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE V5
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Not Provided
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Not Provided
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Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer
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A Randomized, Multicenter, Double-blind Phase 3 Study of Amcenestrant (SAR439859) Plus Palbociclib Versus Letrozole Plus Palbociclib for the Treatment of Patients With ER (+), HER2 (-) Breast Cancer Who Have Not Received Prior Systemic Anti-cancer Treatment for Advanced Disease
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Primary Objective:
To determine whether Amcenestrant (SAR439859) in combination with palbociclib improvesprogression free survival (PFS) when compared with letrozole in combination with palbociclib in participants with ER+, HER2- advanced breast cancer who have not received any prior systemic anticancer therapies for advanced disease.
Secondary Objective:
- To compare the overall survival in both treatment arms
- To evaluate the objective response rate in both treatment arms
- To evaluate the duration of response in both treatment arms
- To evaluate the clinical benefit rate in both treatment arms
- To evaluate progression-free survival on next line of therapy
- To evaluate the pharmacokinetics of amcenestrant, and palbociclib
- To evaluate health-related quality of life in both treatment arms
- To evaluate the time to first chemotherapy in both treatment arms
- To evaluate safety in both treatment arms
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Study duration per participant is approximately 59 months, which includes a 33- month treatment period
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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Breast Cancer
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- Drug: Amcenestrant-matching placebo
Pharmaceutical form: Tablets Route of Administration: Oral
- Drug: SAR439859
Pharmaceutical form: Tablets Route of Administration: Oral
Other Name: Amcenestrant
- Drug: Palbociclib
Pharmaceutical form: Capsules/Tablets Route of Administration: Oral
Other Name: Ibrance
- Drug: Letrozole
Pharmaceutical form: Tablets Route of Administration: Orally
- Drug: Goserelin
Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous
- Drug: Letrozole-matching placebo
Pharmaceutical form: Tablets Route of Administration: Orally
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- Experimental: Amcenestrant with Letrozole-matching placebo Arm
Participants in Amcenestrant with Letrozole-matching placebo Arm will be administered: Amcenestrant dose, once daily, continuously. Letrozole-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle. Goserelin once every 4 weeks in pre/peri menopausal women and men
Interventions:
- Drug: SAR439859
- Drug: Palbociclib
- Drug: Goserelin
- Drug: Letrozole-matching placebo
- Active Comparator: Letrozole with Amcenestrant matching placebo Arm
Participants in Letrozole with Amcenestrant-matching placebo Arm will be administered: Letrozole dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle Goserelin once every 4 weeks in pre/peri menopausal women and men
Interventions:
- Drug: Amcenestrant-matching placebo
- Drug: Palbociclib
- Drug: Letrozole
- Drug: Goserelin
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Bardia A, Cortes J, Hurvitz SA, Delaloge S, Iwata H, Shao ZM, Kanagavel D, Cohen P, Liu Q, Cartot-Cotton S, Pelekanou V, O'Shaughnessy J. AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer. Ther Adv Med Oncol. 2022 Mar 15;14:17588359221083956. doi: 10.1177/17588359221083956. eCollection 2022.
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Active, not recruiting
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1068
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708
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December 29, 2023
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June 28, 2022 (Final data collection date for primary outcome measure)
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Inclusion criteria :
- Adult participants with loco-regional recurrent or metastatic disease not amenable to curative treatment
- Confirmed diagnosis of ER+/HER2- breast cancer
- No prior systemic treatment for loco-regional recurrent or metastatic disease
- Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Participants should be willing to provide tumor tissue
- Capable of giving informed consent
Exclusion criteria:
- Known active brain metastases
- Prior neo (adjuvant) treatment with any selective estrogen receptor degrader (SERD)
- Inadequate organ and marrow function
- Disease recurrence while on, or within 12 months of completion of (neo)adjuvant endocrine therapy
- Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods
- Male participants who disagree to follow contraception
- Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term
- Participants with significant concomitant illness
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Estonia, Finland, France, Georgia, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Puerto Rico, Russian Federation, Singapore, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
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NCT04478266
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EFC15935 2020-001824-33 ( EudraCT Number ) U1111-1233-0486 ( Other Identifier: UTN )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org |
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Sanofi
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Same as current
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Sanofi
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Same as current
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Not Provided
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Study Director: |
Clinical Sciences & Operations |
Sanofi |
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Sanofi
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September 2022
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