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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 367
- 试验地点
- 109
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Estrogen receptor(ER) positive status.
- •Human epidermal growth factor receptor 2 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 Cyclin-dependent kinase 4 and 6(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.
排除标准
- •Eastern Cooperative Oncology Group performance status =>
- •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 greater than 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 Uridine'5 Diphospho-Glucuronosyl Transferase(UGT) less than 2 weeks before randomization.
- •Treatment with strong Cytochrome P450 (CYP)3A 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.
研究组 & 干预措施
Amcenestrant
Daily amcenestrant dose administered orally under fed or fast condition
干预措施: Amcenestrant (Drug)
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)
干预措施: Fulvestrant (Drug)
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)
干预措施: Anastrozole (Drug)
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)
干预措施: Letrozole (Drug)
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)
干预措施: Exemestane (Drug)
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)
干预措施: Tamoxifen (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: 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.
Chinese Cohort: Progression Free Survival
时间窗: From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first, up to primary completion date of 15-Feb-2022, a maximum of 121 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 RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
次要结局
- Overall Survival (OS)(From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks))
- 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))
- 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))
- 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))
- 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))
- 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)
- 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))
- 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)
- 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]))
- 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]))
- 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]))
- 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]))
- Chinese Cohort: Overall Survival(From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 183 weeks))
- Chinese Cohort: 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: 183 weeks))
- Chinese Cohort: 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: 183 weeks))
- Chinese Cohort: 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: 183 weeks))
- Chinese Cohort: Duration of Response(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: 183 weeks))
- Chinese Cohort: Progression Free Survival According to Estrogen Receptor 1 Gene 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: 183 weeks))
- Chinese Cohort: Plasma Concentration of Amcenestrant(Cycle 1 Day 1: 1.5 hours(h), 4h post-dose, Cycle 1 Day 15: pre-dose; Cycle 2 Day 1: pre-dose, 1.5h, 4h, 8h post-dose; Cycles 3, 4, and 6 Day 1: pre-dose)
- Chinese Cohort: Within-Participant Steady State Ctrough of Amcenestrant(Pre-dose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1)
- Chinese Cohort: Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Domain Scores(Baseline and up to 183 weeks)
- Chinese Cohort: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Visual Analog Scale Score(Baseline and up to 183 weeks)
- Chinese Cohort: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Health Utility Index Value(Baseline and up to 183 weeks)
- Chinese Cohort: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module Domain Scores(Baseline and up to 183 weeks)
- Main Cohort and Chinese Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From first dose of study treatment (Cycle 1 Day 1) up to 152 weeks for main cohort and 183 weeks for Chinese cohort)