Phase I/II Study of the PI3K Inhibitor TL117 Alone and in Combination With Paclitaxel in Patients With Relapsed/Metastatic Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Phase Ia -Dose Limiting Toxicity (DLT) of TL117 treatment
研究概览
简要总结
The purpose of this study is to assess the safety, pharmacokinetic and efficacy of TL117 plus paclitaxel in patients with recurrent or metastatic head and neck cancer.
详细描述
This is a Phase 1/2 open label, single arm study, and is divided into three phases: the single-agent dose-escalation phase Ia trial, the TL117 plus paclitaxel dose-escalation phase Ib trial, and the open label, multicenter phase 2 trial of TL117 plus paclitaxel.
Adverse events and dose limiting toxicities will be assessed from the first dose of study drug though day 28. When the maximum tolerated dose (MTD) of TL117 plus paclitaxel is determined, additional patients will be treated at the defined RP2D dose until occurrence of unacceptable toxicity, disease progression or withdrawal of consent or death.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-70 years old for Phase 1a, 18-75 years old for Phase 1b and 2;
- •Histologically and/or cytologically confirmation of recurrent/metastatic squamous cell carcinoma of the head and neck;
- •At least one evaluable or measurable tumor lesion;
- •Adequate performance status;
- •A minimum life expectancy of > 3 months;
- •Adequate cardiac, kidney, and liver function;
- •Willingness of all subjects of childbearing potential to use acceptable methods of birth control;
排除标准
- •Any chemotherapy, radiotherapy, targeted therapy, immunotherapy, endocrine therapy and other systematic anti-tumor therapies within 4 weeks prior to the first dose of the study drug (some exceptions apply)
- •Prior or current PI3K inhibitor therapy;
- •Type 1 or type 2 diabetes requiring antihyperglycemic medication;
- •Major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the first dose, or required elective surgery during the study period;
- •Any unresolved toxicities from prior therapy greater than Grade 1;
- •Inability to swallow, or serious gastrointestinal absorption conditions;
- •History of immunodeficiency;
- •Active central nervous system metastases;
- •Active hepatitis B or C virus infection;
- •Uncontrolled active infection;
- •Serious cardiovascular disease；
- •Clinically uncontrollable effusion in the third space;
- •Known allergy and/or contraindications to paclitaxel;
- •Known alcohol or drug dependence;
- •Mental disorders or poor compliance;
- •Pregnant or lactating women;
研究组 & 干预措施
Single arm, open label
Phase 1a: All subjects receiving TL117 alone (20-120 mg); Phase 1b: All subjects receiving TL117 (MTD-1 or MTD) plus Paclitaxel; Phase 2: All subjects receiving TL117 in combination with Paclitaxel at RP2D
干预措施: TL117 (Drug)
Single arm, open label
Phase 1a: All subjects receiving TL117 alone (20-120 mg); Phase 1b: All subjects receiving TL117 (MTD-1 or MTD) plus Paclitaxel; Phase 2: All subjects receiving TL117 in combination with Paclitaxel at RP2D
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Phase Ia -Dose Limiting Toxicity (DLT) of TL117 treatment
时间窗: From time of the first dosing to time of Cycle 1 Day 28（each cycle is 28 days）
Per DLT criteria as defined in protocol
Phase Ib -Dose Limiting Toxicity (DLT) of TL117 plus paclitaxel combination treatment
时间窗: From time of the first dosing to time of Cycle 1 Day 28（each cycle is 28 days）
Per DLT criteria as defined in protocol
Phase II - Objective response rate (ORR)
时间窗: Every 8 weeks from date of first treatment until date of last treatment up to 12 months
Objective response rate (ORR): percentage of patients with best overall response of complete response (CR) and partial response (PR) according to RECIST v1.1.
次要结局
未报告次要终点