A Phase I Study of HS-10516 in Patients With VHL Syndrome Associated Tumors，to Investigate Safety, Tolerance, Pharmacokinetic and Efficacy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Phase Ia: MTD/MAD of HS-10516
研究概览
简要总结
The aim of the Phase Ia portion is to identify the maximum tolerated dose or maximum acceptable dose MTD/MAD of HS-10516. The phase Ib portion will evaluate the preliminary efficacy of HS-10516 in patients with VHL Syndrome Associated Tumors.
详细描述
This is a Phase Ia/Ib open label multicenter study of HS-10516 in Chinese patients aged 18 years or older with VHL Syndrome Associated Tumors. HS-10516 as a single agent, is administrated orally once daily. The aim of phase Ia, a dose escalation study, is to identify the MTD/MAD of HS-10516. The goal of Phase Ib, a dose expansion study, is to evaluate the safety, pharmacokinetics and antitumor efficacy of HS-10516.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female from 18 to 80 year-old
- •Patients with advanced clear cellrenal cell carcinoma or von Hippel-Lindau Syndrome associated tumors
- •Has an Eastern Cooperative Oncology Group performance status of 0-1
- •Has a life expectancy of ≥ 12 weeks
- •Should use adequate contraceptive measures throughout the study
- •Females subject must not be pregnant at screening
- •Has the ability to understand and willingness to sign a written informed consent before the performance of the study.
排除标准
- •Recieved or being received treatment as follows:
- •Hypoxia-induced factor inhibitors
- •Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
- •Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment
- •Colony-stimulating factors (CSFs) within 4 weeks before the first dose of study treatment
- •Local radiotherapy within 2 weeks prior to the first dose of study treatment; more than 30% of bone marrow radiotherapy or large-area irradiation within 4 weeks before the first dose of study treatment.
- •Major surgery within 4 weeks prior to the first dose of study treatment.
- •Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- •Has failed to recover from a ≥ grade 2 adverse event due to prior anti-tumor therapy
- •Has another malignancy or a history of another non-VHL syndrome associated malignancy
- •Has inadequate bone marrow reserve or organ dysfunction
- •Has a clinically significant bleeding events or tendency within 1 month prior to the first dose of study treatment
- •Has severe infections within 4 weeks prior to the first dose of study treatment
- •Has digestive system diseases may influencing ADME of study drug
- •Has a history of severe hypersensitivity reaction, or proven allergic to HS-10516 or its metabolin
- •Has any disease or condition would compromise subject safety or interfere with study assessments by investigator's decision
研究组 & 干预措施
Phase Ia dose escalation arm
Participants will be assigned to pre-specified dose level to identify the MTD/MAD of HS-10516.
干预措施: Oral HS-10516 (Drug)
Phase Ib dose expansion arm 1
Participants with VHL Syndrome associated RCC, whose lesions diameter ≤ 3 cm.
干预措施: Oral HS-10516 (Drug)
Phase Ib dose expansion arm 2
Participants with VHL Syndrome associated RCC, who could not be included in arm 1.
干预措施: Oral HS-10516 (Drug)
Phase Ib dose expansion arm 3
Participants with VHL Syndrome associated non-RCC tumors.
干预措施: Oral HS-10516 (Drug)
结局指标
主要结局
Phase Ia: MTD/MAD of HS-10516
时间窗: Approximately 2 months
Maximum Tolerated Dose or Maximum Acceptable Dose determined by the Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 35 days of dosing) in the Dose Escalation Phase
Phase Ib: Objective Response Rate (ORR) by Independent Review Committee (IRC)
时间窗: Approximately 1 year
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR will be assessed by IRC.
次要结局
- Observed maximum plasma concentration (Cmax) of HS-10516(Approximately 2 months)
- Time to reach maximum plasma concentration (Tmax) of HS-10516(Approximately 2 months)
- ORR by investigators/IRC per system(Approximately 1 year)
- Overall Survival (OS)(Approximately 2 years)
- Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-10516(Approximately 1 year)
- Progression Free Survival (PFS) by investigators/IRC per system(Approximately 2 years)
- Duration of Response (DoR) by investigators/IRC per system(Approximately 1 year)
- The Number of Participants with Adverse Events(Approximately 2 years)
- Disease Control Rate (DCR) by investigators/IRC per system(Approximately 1 year)