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临床试验/NCT05949541
NCT05949541
招募中
2 期

Study of Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- (Open, Randomized, Phase II )

Fudan University1 个研究点 分布在 1 个国家目标入组 265 人2023年7月26日

概览

阶段
2 期
干预措施
Everolimus 10 mg
疾病 / 适应症
Breast Cancer
发起方
Fudan University
入组人数
265
试验地点
1
主要终点
Progression Free Survival (PFS)
状态
招募中
最后更新
2年前

概览

简要总结

This is a randomized, controlled, open-label, phase II study to explore the efficacy and safety of Everolimus in combination with standard first-line endocrine therapy for the HR+/ HER2-SNF1 subtype of advanced breast cancer. The study was used to explore the efficacy of Everolimus in combination with standard endocrine therapy.

详细描述

A total of 584 patients with luminal breast cancer who received surgery in the breast surgery Department of the Affiliated Cancer Hospital of Fudan University were collected in the early stage. All patients could be divided into four categories, namely SNF1 (classical luminal type), SNF2 (immune-mediated type), SNF1 (proliferative type), and SNF4 (receptor tyrosine kinase-driven type), through clustering by the SNF algorithm. SNF1 (classical luminal type): The transcriptional component type is dominated by PAM50 LumA, with high PIK3CA mutation and low TP53 mutation. By combining artificial intelligence based on H\&E pathological sections with deep learning methodology, molecular typing can be effectively distinguished. Prior to enrollment, the patient's primary lesion or metastasis was classified by molecular classification based on the H\&E section combined with digital pathology, and SNF1 was confirmed to be considered for subsequent enrollment. Receivers will be randomly assigned 1:1 to either Everolimus plus Standard Endocrine therapy (study group) or Standard Endocrine therapy (control group). Treatment will continue until disease progression, intolerable toxicity, informed withdrawal, or death from any cause.

注册库
clinicaltrials.gov
开始日期
2023年7月26日
结束日期
2028年1月
最后更新
2年前
研究类型
Interventional
研究设计
Parallel
性别
Female

研究者

责任方
Principal Investigator
主要研究者

Zhimin Shao

Director of General Surgery of Fudan Shanghai Cancer Center

Fudan University

入排标准

入选标准

  • Patients need to meet all of the following conditions
  • Patients must be ≥18 and ≤ 75 years of age;
  • Pathologically confirmed breast cancer is HR+/HER2- breast cancer (IHC ER \>10%, or/and PR\>10%, HER 0 OR +, if HER2++, FISH negative);
  • SNF1 subtype definition: SNF1 subtype confirmed by digital pathology of H\&E sections;
  • Locally advanced breast cancer (radical local therapy is not possible) or metastatic breast cancer (without using adjuvant CDK4/6 inhibitors in the past, or one year after adjuvant CDK4/6 inhibitor therapy has ended);
  • No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer;
  • Patients with at least one measurable lesion that has not previously received radiation therapy and can be evaluated repeatedly according to RECIST 1.1;
  • The functions of the main organs are basically normal, and the following conditions are met:
  • Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L;
  • Biochemical examination shall meet the following standards: TBIL≤1.5×ULN (upper limit of normal value); ALT and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula);

排除标准

  • Patients with any of the following conditions were excluded from the study
  • Patients with central nervous system metastasis out of control (symptoms need to use glucocorticoids or mannitol).
  • A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia;
  • Radiotherapy, chemotherapy, surgery, other targeted therapy and immunotherapy for advanced HR+/HER2- breast cancer within 4 weeks prior to first administration of drugs used in this study.
  • Pregnant or lactating patients;
  • Other malignancies within the previous 3 years, excluding cured skin basal cell carcinoma and cervical carcinoma in situ;
  • Significant comorbid medical conditions, including mental illnesses that the investigator or sponsor believes would adversely affect the patient's participation in the study;
  • Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies;
  • The investigator does not consider the patient suitable for participation in any other circumstances of the study.

研究组 & 干预措施

Arm-A

Everolimus + CDK4/6 inhibitor+ Endocrine therapy group: Everolimus, 10mg po. qd; Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

干预措施: Everolimus 10 mg

Arm-A

Everolimus + CDK4/6 inhibitor+ Endocrine therapy group: Everolimus, 10mg po. qd; Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

干预措施: CDK4/6 Inhibitor SHR6390

Arm-A

Everolimus + CDK4/6 inhibitor+ Endocrine therapy group: Everolimus, 10mg po. qd; Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

干预措施: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors

Arm-B

CDK4/6 inhibitor+ Endocrine therapy group: Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

干预措施: CDK4/6 Inhibitor SHR6390

Arm-B

CDK4/6 inhibitor+ Endocrine therapy group: Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

干预措施: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors

结局指标

主要结局

Progression Free Survival (PFS)

时间窗: Approximately 5 years

The interval from randomization until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first.

次要结局

  • Objective Response Rate (ORR)(Approximately 5 years)
  • Overall Survival (OS)(Approximately 5 years)
  • Clinical Benefit Rate (CBR)(Approximately 5 years)
  • Safety and tolerability(Approximately 5 years)

研究点 (1)

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