Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Albumin-bound Formulation of Docetaxel for Intravenous Infusion in Patients With Advanced Solid Tumors: A Phase 1, Single-center, Open-label, Dose-escalation Study
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 208
- 试验地点
- 1
- 主要终点
- Number of participants who experienced AE during cycle1.
研究概览
简要总结
This trial is an open-label, single-center, dose-escalation and cohort-expansion Phase I clinical study in patients with advanced solid tumors. The aim of this study is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of albumin-bound formulation of docetaxel for intravenous infusion in patients with advanced solid tumors.
详细描述
This study was conducted in two stages. The first stage (Stage I) is a dose-escalation study. A classic 3+3 design will be used to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Patients with advanced solid tumors will be assigned to receive sequentially higher doses of albumin-bound formulation of docetaxel once every three weeks (a Cycle) by intravenous infusion, starting at a dose of 50mg/m2. Patients will receive the albumin-bound formulation of docetaxel
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
- •Age ≥18, ≤75 years, no gender limitation；
- •Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors, for which standard therapy either does not exist or has proven to be ineffective, intolerable or unacceptable for the patient；
- •At least one measurable lesion as per RECIST version 1.1；
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1；
- •Life expectancy ≥3 months；
- •Adequate bone marrow, cardiac, liver and renal function；
排除标准
- •Chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks of the first dose of the study drug, 6 weeks for mitomycin C or nitrosoureas, 2 weeks (or 5 half-lives whichever is longer) for using fluorouracil or small molecule targeted drugs, 2 weeks for using traditional Chinese medicine with anti-tumor indications；
- •Currently enrolled in any other clinical study, or administration of other investigational agents w
研究组 & 干预措施
Experimental: solid tumors
Albumin-bound docetaxel by intravenous infusion.Patients receive albumin-bound docetaxel once every three weeks (a Cycle), starting at a dose of 50mg/m2.
干预措施: Albumin-bound docetaxel (Drug)
结局指标
主要结局
Number of participants who experienced AE during cycle1.
时间窗: 21 days.
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Number of participants who experienced DLT during cycle1.
时间窗: 21 days.
A DLT was graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.02 and defined as any of the following: grade 3 or 4 non-hematologic adverse events unless they were not optimally treated with supportive care; grade 3 or 4 asymptomatic laboratory abnormal values lasting \>7 days; prolonged grade 2 toxicity (lasting more than 2 weeks) leading to treatment interruption and/or dose reduction; pancytopenia with a hypocellular bone marrow and no marrow blasts lasting ≥6 weeks (AL participants); grade 3 neutropenia with fever or infection (OHM participants); grade 3 thrombocytopenia with bleeding (OHM participants); or grade 4 neutropenia or thrombocytopenia, regardless of symptoms and lasting ≥3 days (OHM participants).
Classic 3+3 design to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)
时间窗: Through study completion, an average of 1 year.
The maximum tolerated dose (MTD) (if available) and recommended Phase 2 dose (RP2D) of Albumin-bound Docetaxel.
次要结局
- Area under the concentration-time curve of Albumin-bound Docetaxel from time 0 to infinity (AUC 0-∞)(21 days.)
- Duration of response (DOR)(Through study completion, an average of 1 year.)
- Observed maximum concentration (Cmax )of Albumin-bound Docetaxel(21 days.)
- Apparent terminal Half-Life (t1/2) of Albumin-bound Docetaxel(21 days.)
- Objective response rate (ORR)(Through study completion, an average of 1 year.)
- Area under the concentration-time curve of Albumin-bound Docetaxel from time 0 to last (AUC 0-∞)(21 days.)
- Apparent total body clearance (CL/F) of Albumin-bound Docetaxel(21 days.)
- Time to maximum concentration (Tmax) of Albumin-bound Docetaxel(21 days.)
- Progression free survival (PFS)(Through study completion, an average of 1 year.)
- Disease control rate (DCR)(Through study completion, an average of 1 year.)