A Phase IB/II to Evaluate Efficacy and Safety of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 4
- 主要终点
- Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1
研究概览
简要总结
This is a phase IB/II clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Letrozole or Anastrozole or Fulvestrant. Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have not received systemic anticancer therapy are eligible for study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer.
- •Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should receive Ovary castration.
- •Inclusion Criteria
- •Cohort 1 and Cohort 2 :No prior systemic anti-cancer therapy for advanced HR+ disease.
- •Cohort 3 and Cohort 4 : Patients must satisfy the following criteria for prior therapy:
- •a) Progressed after 2 years during treatment of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.
- •b)Progressed within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.
- •c) Progressed while 6 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for advanced/metastatic breast cancer if pre- or perimenopausal.
- •One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy.
- •Eastern Cooperative Oncology Group [ECOG] 0-1 Measurable disease as per Response Evaluation Criterion in Solid Tumors[RECIST] 1.1
- •Adequate organ and marrow function
- •Exclusion Criteria
- •Confirmed diagnosis of HER2 positive disease
- •Patients who received any endocrine therapy as neo/adjuvant therapy for breast cancer are eligible. If the neo/adjuvant therapy of any endocrine therapy , the disease-free interval must be greater than 12 months from the completion of treatment until study entry.
- •Patients who received prior treatment with any CDK4/6 inhibitor, everolimus,fulvestant.
- •Clinically significant cardiovascular and cerebrovascular diseases,including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), or ventricular arrhythmia which need medical intervention.
- •Has known active central nervous system metastases.
排除标准
- 未提供
研究组 & 干预措施
Cohort 1 (Part 1)
Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
干预措施: SHR6390 (Drug)
Cohort 1 (Part 1)
Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
干预措施: Letrozole or anastrozole or Fulvestrant (Drug)
Cohort 2 (Part 1)
SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
干预措施: SHR6390 (Drug)
Cohort 2 (Part 1)
SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
干预措施: Letrozole or anastrozole or Fulvestrant (Drug)
SHR6390 + Letrozole or anastrozole (Part 2)
SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
干预措施: SHR6390 (Drug)
SHR6390 + Letrozole or anastrozole (Part 2)
SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
干预措施: Letrozole or anastrozole or Fulvestrant (Drug)
SHR6390 + Fulvestrant Cohort 3 (Part 1)
SHR6390 (at protocol defined dose levels), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily
干预措施: SHR6390 (Drug)
SHR6390 + Fulvestrant Cohort 3 (Part 1)
SHR6390 (at protocol defined dose levels), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily
干预措施: Letrozole or anastrozole or Fulvestrant (Drug)
SHR6390 + Fulvestrant Cohort 4 (Part 1)
SHR6390 (TBD), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily
干预措施: SHR6390 (Drug)
SHR6390 + Fulvestrant Cohort 4 (Part 1)
SHR6390 (TBD), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily
干预措施: Letrozole or anastrozole or Fulvestrant (Drug)
结局指标
主要结局
Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1
时间窗: Up to 4 weeks
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. Up to 24 months.
次要结局
- Area under the plasma concentration versus time curve (AUC) of SHR6390(Up to 4 weeks)
- The time of SHR6390 to reach the maximum concentration (Tmax)(Up to 4 weeks)
- Progression-free Survival (PFS) per RECIST 1.1(Up to approximately 24 months.)
- Peak Plasma Concentration (Cmax) of SHR6390(Up to 4 weeks)
- Half-time (t1/2) of SHR6390(Up to 4 weeks)
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(Up to approximately 24 months.)
- Disease Control Rate (DCR) per RECIST 1.1(Up to approximately 24 months.)
- Number of Participants With adverse events (AEs) and serious adverse events (SAEs)(Up to approximately 24 months.)