Amcenestrant (SAR439859) plus palbociclib as first line therapy for patients with ER(+) HER2(-) advanced breast cancer

JRCT ID: jRCT2031200210

Registered date:20/11/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Breast Cancer
• Date of first enrollment: 02/12/2020
• Target sample size: 1066
• Countries of recruitment: Australia,Japan,Belgium,Japan,Canada,Japan,Chile,Japan,France,Japan,Hungary,Japan,Italy,Japan,Republic of Korea,Japan,Netherlands,Japan,Russian Federation,Japan,Singapore,Japan,Spain,Japan,Ukraine,Japan,United States,Japan,Argentina,Japan,Austria,Japan,Brazil,Japan,Bulgaria,Japan,China,Japan,Czechia,Japan,Finland,Japan,Georgia,Japan,Germany,Japan,Poland,Japan,Portugal,Japan,South Africa,Japan,Turkey,Japan,United Kingdom,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

- Drug: Amcenestrant (SAR439859)
Pharmaceutical form: Tablets, Route of administration: Oral
- Drug: Amcenestrant-matching placebo
Pharmaceutical form: Tablets, Route of administration: Oral
- Drug: Letrozole
Pharmaceutical form: Capsules, Route of administration: Oral
- Drug: Letrozole-matching placebo
Pharmaceutical form: Capsules, Route of administration: Oral
- Drug: Palbociclib (Ibrance)
Pharmaceutical form: Capsules/Tablets, Route of administration: Oral
- Drug: Goserelin
Pharmaceutical form: Depot Injection, Route of administration: Subcutaneous

Outcome(s)

Primary Outcome

1. 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.

Secondary Outcome

1. 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)
2. 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
3. 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.
4. 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
5. PK parameter: Plasma concentrations [Time Frame: From randomization date to end of treatment (up to approximately 4 years)]
Plasma concentrations of Amcenestrant and palbociclib.
6. 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
7. 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.
8. 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)
9. 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)
10. 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
11. 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
12. 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.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Female

Include 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 nonmeasurable 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

Exclude 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 childbearing potential unwilling to use recommended contraception methods
- Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term
- Participants with significant concomitant illness

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT04478266,2020-001824-33