A Phase Ⅰ Study of PI3K/mTOR Dual Inhibitor WXFL10030390 to Evaluate the Safety, Tolerability and Pharmacokinetics in Patients With Advanced Solid Tumors or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0
研究概览
简要总结
WXFL10030390 (WX390) is a novel oral small molecular that inhibits phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) and has demonstrated potent inhibitory effects on multiple human tumor xenografts. The first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of WX390 at single dose and multiple doses.
详细描述
This study will be an open-lable, phase Ⅰ study and will evaluate the safety and pharmacokinetics of WX390 after a single administration followed by a 28-day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-lable administration of WX390 at the MTD.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 and ≤75 years of age
- •Histological or cytological confirmed advanced solid tumor or lymphoma, standard regimen failed or no standard regimen available
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Life expectancy of more than 3 months
- •At least one measurable lesion according to RECIST 1.1 or Lugano 2014
- •Adequate organic function: Absolute neutrophil count (ANC) ≥2.0×109/L，PLT≥100×109/L，Hb≥9g/L hepatic function:TBIL≤1.5×upper limit of normal (ULN)，Alanine aminotransferase (ALT) ≤2.5×ULN，aspartate aminotransferase (AST) ≤2.5×ULN; renal function:Cr≤1.5×ULN and>50ml/min; coagulation function: APTT≤1.5 ×ULN，PT≤1.5 ×ULN, INR≤1.5 ×ULN; GLU<7mmol/L and HbA1C<7%; TG≤1.5×ULN，CHOL≤1.5×ULN
- •Subjects who have the fertility should agree to use reliable contraceptive methods during this study and subsequently at least 12 weeks after the last administration; for female subjects, the blood pregnancy test should be negative within 7 days prior to the enrollment
- •Signed and dated informed consent
排除标准
- •Anti-cancer therapy within 4 weeks prior to the initiation of investigational treatment
- •Surgery within 4 weeks prior to the initiation of study treatment
- •Use of strong inducers or inhibitors of CYP3A4 within 1 weeks before the first dose of study treatment. See Appendix 5 for a list of such medications
- •Received corticosteroids treatment or other immunodepressant within 2 weeks before the first dose of study treatment
- •Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for alopecia)
- •Patients with clinical symptomatic brain metastases, spinal compression, meningitis carcinomatosa or other evidence that shows uncontrolled brain or spinal metastases
- •Previous treatment with PI3K/mTOR inhibitors
- •Patients who once or being suffer Interstitial lung disease
- •Evidence of ongoing or active infection
- •History of human immunodeficiency virus (HIV) infection
- •History of hepatitis B or C infection
- •Clinically significant cardiovascular disease, including but not limited to acute coronary syndrome, congestive heart-failure, cerebral stroke within 6 months prior to enrollment, New York Heart Association Class ≥II cardiac functional grading or left ventricular ejection fraction (LVEF) < 50%
- •Inability to take medication orally
- •Severe gastrointestinal disease leading to diarrhea
- •Diabetics receiving insulin treatment
- •Patients with active autoimmune disease (including systemic lupus erythematosus, rheumatoid arthritis, nodular vasculitis)
- •Abuse of alcohol or drugs
- •People with cognitive and psychological abnormality or with low compliance
- •Pregnant or lactating women
- •Researchers believe that subjects may not be able to complete the study or may not be able to comply with the requirements of this study
研究组 & 干预措施
WXFL10030390 tablet
WXFL10030390 continuous oral dosing (0.1 mg once a day)
WXFL10030390 continuous oral dosing (0.2 mg once a day)
WXFL10030390 continuous oral dosing (0.4 mg once a day)
WXFL10030390 continuous oral dosing (0.7 mg once a day)
WXFL10030390 continuous oral dosing (1.1 mg once a day)
WXFL10030390 continuous oral dosing (1.4 mg once a day)
WXFL10030390 continuous oral dosing (1.7 mg once a day)
干预措施: WXFL10030390 (Drug)
结局指标
主要结局
Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0
时间窗: From first dose to within 30 days after the last dose
The safety and tolerability of WXFL10030390 will be evaluated based on adverse events data. Other safety parameters include physical examination, clinical laboratory tests including coagulation function, renal function, hepatic function, blood glucose and blood lipid.
次要结局
- Objective response rate(From first dose to within 30 days after the last dose)
- Maximum plasma concentration (Cmax)(28 days)
- Area under the plasma concentration-time curve (AUC)(28 days)
- Terminal elimination half-life (t½)(28 days)
- Disease control rate(From first dose to within 30 days after the last dose)
- Time to reach plasma Cmax (tmax)(28 days)
- Recommended study Phase II dose (RP2D)(Up to 1 year)