A Phase Ⅰb Study Evaluating the Safety, Tolerability and Pharmacokinetics of Pegylated Recombinant Human Endostatin (PEG-ENDO) in Subjects With Advanced / Metastatic Non-small Cell Lung Cancer (NSCLC) or Other Solid Tumors
试验速览
- 阶段
- 1 期
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
The primary purpose of this study is to examine the safety, tolerability and pharmacokinetics of PEG-ENDO in combination with docetaxel in subjects previously treated or untreated (standard therapy is not suitable or without standard therapy) for advanced or metatatic non-small cell lung cancer (NSCLC) or other solid tumors.
详细描述
This is a multicenter, open-label, dose-escalation study in subjects with advanced or metatatic non-small cell lung cancer (NSCLC) or other solid tumors.There will be five cohorts planning as following:
cohort 1: PEG-ENDO 1 mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 2: PEG-ENDO 2mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 3: PEG-ENDO 4 mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 4: PEG-ENDO 6 mg/kg+Docetaxel75 mg/m2,once every 3 weeks at day 1 cohort 5: PEG-ENDO 8 mg/kg+Docetaxel75 mg/m2, once every 3 weeks at day 1
* Every 3 weeks as a treatment cycle. Subjects received only PEG-ENDO in the first cycle. For second cycle or the higher, they received a combination therapy of PEG-ENDO and docetaxel. Docetaxel was limited in 4 or 6 cycles。 The observation period of DLT was the 21 days after the first administration of PEG-ENDO. During the observation period of DLT (cycle 1), subjects only receive the corresponding dose of PEG-ENDO , for the second cycle and higher ,they will treated with the combination of PEG-ENDO and Docetaxel until disease progression (PD) or intolerance . Docetaxel was limited in 4 or 6 cycles。
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
- •Provision of signed and dated, written informed consent.
- •18-70years old, male or female.
- •Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer(NSCLC) or other solid tumor, previous treated with standard therapy , or standard therapy not suitabl ,or without standard therapy.
- •At least one measurable disease according to RECIST v1.
- •Life expectancy of at least 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance score 0 or
- •Demonstrate adequate organ function -
排除标准
- •uncontrolled primary CNS tumors, brain metastases, or meningeal metastases.
- •Evidence of a tumor that compresses or invades major blood vessels.
- •History of hemoptysis (>1/2 teaspoon per event) or severe bleeding or evidence of bleeding disorders in the last 3 months.
- •Clinically significant active cardiovascular disease within 6 months prior to planned start of PEG-ENDO.
- •Prior treatment with anti-agiogenetic agent.
- •Pregnant female patients; breastfeeding female patients.
研究组 & 干预措施
PEG-ENDO+Docetaxel
PEG-ENDO( 1 mg/kg or 2mg/kg or 4mg/kg or 6mg/kg or 8mg/kg）+Docetaxel 75 mg/m2，once every 3 weeks at day 1
干预措施: Pegylated Recombinant Human Endostatin（PEG-ENDO） (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: First 21days for dosing（Cycle1，each cycle is 21 days)
Incidence of Dose Limiting Toxicity
Adverse Event(AE)
时间窗: From the time the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
Incidence of Adverse Events
Serious Adverse Event(SAE)
时间窗: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
Incidence of Serious Adverse Events
Laborarory test abnormality
时间窗: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
Incidence of clinically significant laboratory abnormalities
Vital signs abnormality
时间窗: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
Incidence of vital signs abnormalities
Electrocardiogram(ECG) abnormality
时间窗: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
Incidence of clinically significant ECG abnormalities
Serum concentration
时间窗: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
Serum concentration of PEG-ENDO
The maximum (or peak) serum ,Cmax
时间窗: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
Cmax of PEG-ENDO following dose concentration.
AUC
时间窗: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
The area under the plot of serum concentration of drug (not logarithm of the concentration) against time after drug administration.
other PK parameters
时间窗: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
The other PK parameters (if applicable).
Maximum Tolerated Dose(MTD)
时间窗: First 21days for dosing（Cycle1，each cycle is 21 days)
To determine the Maximum Tolerated Dose (MTD) of PEG-ENDO in subjects with Advanced / Metastatic NSCLC or Other Solid Tumors
次要结局
- Overall Response Rate(ORR)(at least 12 weeks)
- Duration of Response(DOR)(Estimated at 4 months after fist documented PD or CR)
- Progression-free survival (PFS)(Estimated at 4 months.)