A Phase III, Multicenter, Open-label Study of Ribociclib vs. Palbociclib in Patients With Advanced Hormone Receptor-positive/HER2-negative/HER2-Enriched Breast Cancer - HARMONIA Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 61
- 试验地点
- 141
- 主要终点
- Progression-free survival
研究概览
简要总结
HARMONIA is an international, multicenter, randomized, open-label and phase III study. The primary objective of this study is to demonstrate that the combination of ribociclib with endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine therapy (letrozole or fulvestrant) in prolonging progression-free survival in patients with advanced HR+/HER2- and HER2-E breast cancer. The study will enroll approximately 456 patients with HER2-E disease from approximately 95 sites worldwide.
In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel +/- Tislelizumab. This cohort does not have a predefined sample size and the objective is only exploratory, given the suggested lack of efficacy of the combinations of hormone therapy and CDK4/6 inhibitors in this subgroup of patients. Enrolment into the basal-like cohort will stop once the HER2-E disease cohort is fully enrolled.
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
- None
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
- •Main Inclusion Criteria:
- •Histologically documented HR-positive and HER2-negative breast cancer by local testing
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
- •Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period.
- •HER2-E or Basal-like subtype as per central PAM50 analysis.
- •Measurable disease or non-measurable disease, as defined by RECIST v1.1
- •Adequate hematologic and end-organ function
- •Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
- •Women of childbearing potential must have confirmed negative serum pregnancy test within 7 days prior to randomization.
- •Women of CBP must be willing to use highly effective methods of contraception.
- •Patient must have a 6-lead or 12-lead ECG with ALL of the following parameters at screening:
- •QTcF interval (QT interval using Fridericia's correction) at screening < 450 msec.
- •Resting heart rate 50-90 beats per minute (determined from the ECG).
排除标准
- •Prior therapy with any CDK4/6 inhibitors.
- •Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer
研究组 & 干预措施
Paclitaxel +/- Tislelizumab - Exploratory cohort
Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
干预措施: Paclitaxel +/- Tislelizumab (Drug)
Ribociclib + Endocrine Therapy
Ribociclib + Fulvestrant or Letrozole
干预措施: Ribociclib + Letrozole OR Fulvestrant (Drug)
Palbociclib + Endocrine Therapy
Palbociclib + Fulvestrant or Letrozole
干预措施: Palbociclib + Letrozole OR Fulvestrant (Drug)
结局指标
主要结局
Progression-free survival
时间窗: From date of randomization until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled
using RECIST 1.1 criteria, as assessed by local radiologists/investigators
次要结局
- Time to response and duration of response(time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled)
- Progression-free survival 2(From randomization until documented progression to second line of therapy, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled)
- Overall response and clinical benefit(until disease progression or 24 weeks from treatment start.)
- Overall Survival(until patient death, assessed up to approximately 62 months after the first patient enrolled)
- Adverse events (safety)(from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled)