Efficacy and Safety of Avatrombopag in Cancer Patients With Thrombocytopenia Induced by Targeted Therapy and Immunotherapy Combination Treatment
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percentage of participants' PLT
研究概览
简要总结
To evaluate the efficacy and safety of Avatrombopag in patients with thrombocytopenia induced by targeted therapy and immunotherapy combination treatment, and provide evidence-based medication for the clinical use of Avatrombopag in patients with PC ≤50×109/L
详细描述
This phase II trial is a single-arm, non-randomized and single-center clinical study.
It is estimated that 30 patients who met the study criteria will be enrolled in PUMCH and treated with Avatrombopag. The investigators will follow up and collect subjects' data each month to evaluate the efficacy and safety of treatment. Primary outcome measure is percentage of participants whose PLT reaches ≥75×109/L, or increases by ≥50×109/L or ≥100% from baseline at least once within 20 days of initial treatment.
Secondary outcome measure:1)Number of days required for PLT to reach ≥50×109/L after treatment; 2)Number of days required for PLT to reach ≥75×109/L after treatment; 3)Percentage of subjects without platelet transfusion within 20 days of treatment; 4)Percentage of subjects without clinically relevant bleeding within 20 days of treatment.
Study Type: Interventional. Masking: Open Label.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Each participant must meet all of the following criteria:
- •Male or female, 18~85 years of age;
- •Diagnosis of malignant solid tumor;
- •Participants receiving combined targeted therapy (including but not limited to tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors) with immunotherapy (including but not limited to PD-1 inhibitors and/or PD-L1 inhibitors and/or CTLA-4 inhibitors);
- •Participants experienced grade III or above thrombocytopenia (PC ≤50×109/L) at least once within 48 h of the screening period; No oral platelet-enhancing drugs were given before enrollmen.
- •ECGO performance status ≤2;
- •Blood test:
- •Hemoglobin (Hb) ≥ 9.0 g/dL;
- •Absolute neutrophils count (ANC) ≥ 1,500/μL;
- •Liver and renal functions:
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3*ULN (Upper Limits of Normal);
- •Serum bilirubin ≤ 1.5*ULN;
- •Albumin ≥ 2.5 g/dL;
- •Serum creatinine ≤ 1.5*ULN (CTCAE Grade Ⅰ)
- •Participants able to oral medication;
- •Expected survival time ≥12 weeks during screening period;
- •Participants with negative urine or serum pregnancy test during screening period; fertile potential participants must agree to use contraception for the whole study period and 30 days after discontinuity of investigational product treatment (infertile potential was defined as the condition including hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal ligation and postmenopausal);
- •Participants in the trial is voluntary and must strictly abide by the protocol;
- •Participants must sign the written informed consent form.
排除标准
- •Participants meeting any of the following criteria will be excluded from the study:
- •Participants has any history of active congestive heart failure [New York Heart Association (NYHA) Grade III-IV], symptomatic ischemia, uncontrolled arrhythmia, pericardial disease, or myocardial infarction during the first 4 months of enrollment;
- •Participants finished major operation within less than 28 days and for minor operation within less than 3 days;
- •Participants had clinically significant acute or active bleeding (e.g., gastrointestinal or central nervous system) within 7 days prior to screening;
- •Participants has medical-known hereditary prethrombotic syndrome (such as factor V Leiden mutation, prothrombin G20210A mutation or hereditary antithrombin III deficiency);
- •Participants has a history of arterial or venous thrombosis within 3 months prior to screening;
- •Participants had treatment with heparin and warfarin within 7 days prior to screening;
- •Participants has history of chronic thrombocytopenia or hemorrhagic disease, or thrombocytopenia induced by other reasons besides targeted therapy and immunotherapy combination treatment(e.g., chronic liver disease or immune thrombocytopenic purpura);
- •Participants had the treatment of platelet transfusion within 3 days before enrollment;
- •Participants had administration of platelet growth factor (e.g., rhTPO, rhIL-11, Eltrombopag, or Romiplostim) for the treatment of thrombocytopenia induced by targeted therapy and immunotherapy combination treatment within 2 weeks prior to screening;
- •Participants' thrombocytopenia responded effectively to hormone therapy;
- •Participants are allergic to Avatrombopag or any of its excipients;
- •Participants were in any other clinical trial of investigational product or device within 30 days prior to screening, except for observational study;
- •Participants have any known concomitant history that may impair the safe completion of the study as assessed by the investigator, such as unstable angina, renal failure due to hemodialysis, or active infection requiring intravenous antibiotics;
- •Participants are pregnant or lactating at the time of screening (as demonstrated by a positive serum β-HCG test) or baseline visit (positive urine β-HCG test)
研究组 & 干预措施
Avatrombopag
Avartripopa is a new generation of oral TPO receptor agonist that simulates the biological effects of TPO in vitro and in vivo.
TPO stimulates megakaryocytes through binding and activation of TPO receptor, which is expressed in hematopoietic stem cells, megakaryotic cell lines and platelets.
By binding to the transmembrane region of the thrombopoietin receptor, Ava Tripopa activates the thrombopoietin receptor in humans, stimulates signal transduction and mimics the biological effects of thrombopoietin, leading to an increase in platelet count.
干预措施: Avatrombopag (Drug)
结局指标
主要结局
Percentage of participants' PLT
时间窗: one year
Percentage of participants whose PLT reaches ≥75×109/L, or increases by ≥50×109/L or ≥100% from baseline at least once within 20 days of initial treatment.
次要结局
- Percentage of subjects without platelet transfusion within 20 days of treatment;(one year)
- Number of days required for PLT to reach ≥50×109/L after treatment;(one year)
- Number of days required for PLT to reach ≥75×109/L after treatment;(one year)
- Percentage of subjects without clinically relevant bleeding within 20 days of treatment.(one year)