Description:
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
Title
- Brief Title: Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
EFC15935
- SECONDARY ID:
2020-001824-33
- SECONDARY ID:
U1111-1233-0486
- NCT ID:
NCT04478266
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Amcenestrant-matching placebo | | Letrozole with Amcenestrant matching placebo Arm |
| SAR439859 | Amcenestrant | Amcenestrant with Letrozole-matching placebo Arm |
| Palbociclib | Ibrance | Amcenestrant with Letrozole-matching placebo Arm |
| Letrozole | | Letrozole with Amcenestrant matching placebo Arm |
| Goserelin | | Amcenestrant with Letrozole-matching placebo Arm |
| Letrozole-matching placebo | | Amcenestrant with Letrozole-matching placebo Arm |
Purpose
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
Detailed Description
Study duration per participant is approximately 64 months, which includes a 33- month
treatment period
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Amcenestrant with Letrozole-matching placebo Arm | Experimental | 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 | - SAR439859
- Palbociclib
- Goserelin
- Letrozole-matching placebo
|
| Letrozole with Amcenestrant matching placebo Arm | Active Comparator | 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 | - Amcenestrant-matching placebo
- Palbociclib
- Letrozole
- Goserelin
|
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival |
| Time Frame: | From randomization date to date of first documentation of progression OR death (up to approximately 4 years) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Overall Survival |
| Time Frame: | From randomization date to date of death (up to approximately 6 years) |
| Safety Issue: | |
| Description: | Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause). |
| Measure: | Objective Response Rate |
| Time Frame: | From randomization date to end of treatment (up to approximately 4 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response |
| Time Frame: | From randomization date to end of treatment (up to approximately 4 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Clinical Benefit Rate |
| Time Frame: | From randomization date to end of treatment (up to approximately 4 years) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | PK parameter: Plasma concentrations |
| Time Frame: | From randomization date to end of treatment (up to approximately 4 years) |
| Safety Issue: | |
| Description: | Plasma concentrations of Amcenestrant and palbociclib. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | Incidence of participants with TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE V5 |
| Measure: | Time to First Chemotherapy |
| Time Frame: | From randomization date to end of treatment (up to approximately 4 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | Change From Baseline between treatment comparison Using the European Quality of Life- 5-Dimension 5 Level (EQ-5D 5L). |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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). |
| Measure: | 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) |
| Safety Issue: | |
| Description: | Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR45 (Breast) Questionnaire. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire. |
| Measure: | Progression-free survival on next line of therapy (PFS2) |
| Time Frame: | From randomization date to date of death (up to approximately 6.5 years) |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Sanofi |
Last Updated
June 29, 2021
