Determine MTD and to Evaluate PK, Safety/Tolerability and Efficacy Profiles of Antroquinonol (Hocena®) in NSCLC Patients Refractory to Conventional Treatment Modalities
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- To Determind the Maximum Tolerable Dose for Antroquinonol
研究概览
简要总结
A phase I study to determine the maximum tolerable dose (MTD) and to evaluate pharmacokinetic, safety/tolerability and efficacy profiles of antroquinonol (Hocena®) in non-small cell lung cancer (NSCLC) subjects refractory to conventional treatment modalities
详细描述
- Antroquinonol, a novel cyclohexenone compound, is a purified compound from extract of Antrodia camphorata.
- The pharmacological effects of antroquinonol were postulated to exert its antitumorigenesis effects through interactions to primary targets of epidermal growth factor receptor (EGFR)/Akt/mitogen-activated protein kinase (MAPK).
- In vivo study in NOD/SCID mice with A549 subcutaneous xenografts consistently showed tumor growth suppression after 2 weeks of oral 30 and 60 mg/kg antroquinonol treatment.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 20 years.
- •Diagnosed stage III/IV NSCLC. The grading is determined according to the Tumor-Node-Metastasis (TNM) staging system for lung cancer.
- •Patients with histologically or cytologically proven primary NSCLC with adenocarcinoma or mixed cell type with adenocarcinoma, who have failed on standard treatments.
- •With progressive tumor after two lines of chemotherapy (including one platinum-based) and 1 EGFR-targeted therapy if patient is identified with EGFR mutation or his/her EGFR mutation status is unknown OR having refused further currently approved treatment modalities.
- •Life expectancy ≥ 3 months.
- •Within 1 week of planned first study treatment day, adequate hematopoietic functions are presented: Total white blood cell (WBC) ≥ 3500 cells/mm3 Hemoglobin (Hb) ≥ 9.0 g/dL Platelets ≥ 100,000 cells/mm3 Absolute neutrophil count (ANC) ≥ 1500 /mm3
- •Within 1 week of planned first study treatment day, adequate hepatic and renal functions are presented: Total bilirubin ≤2.0 mg/dLGOLANTA20090911, Amendment 4/v. 1.0/ 13 October 2010 AST ≤ 3 × upper limit of normal (ULN); patients with liver metastasis: AST ≤ 5 × ULN ALT ≤ 3 × ULN; patients with liver metastasis: ALT ≤ 5 × ULN Creatinine ≤ 1.5 mg/dL
- •Must have recovered from toxicities of previous anti-cancer treatments to grade 1 NCI-CTC or better, except for alopecia.
- •Eastern Cooperative Oncology Group (ECOG) performance score ≤
- •Female patient with childbearing potential confirmed of not being pregnant at the screening; and informed that effective contraception must be used during the entire treatment period of this study and for 6 months after exiting from the study.
- •Given signed and dated written informed consent form.
排除标准
- •Primary major surgery < 4 weeks prior to the planned first study treatment day.
- •Lactating, pregnant or plans to be become pregnant.
- •Except for alopecia, recovered from any previous treatments to a grade 1 or less prior to the planned first study treatment day.
- •With active systemic infections, active and clinically significant cardiac diseases, active gastrointestinal ulcers, or medical conditions that may significantly affect adequate absorption of investigational product.
- •Within 5 years, prior history of malignancy other than NSCLC, except cervical carcinoma in situ and basal or squamous cell skin carcinoma.
- •Known allergic to antroquinonol or its formulation excipients.
- •Within 14 days of planned first study treatment day, exposed to any drug(s) known to be significant CYP2C19, 3A4, 2C8, and 2E1, inhibitor or activator.
- •With conditions judged by the investigator as unsuitable for the study.
研究组 & 干预措施
Antroquinonol
6 dose levels, Dose Level 1 (4 weeks) : 50 mg Antroquinonol; Dose Level 2 (4 weeks) : 100mg Antroquinonol; Dose Level 3 (4 weeks) : 200mg Antroquinonol; Dose Level 4 (4 weeks) : 300mg Antroquinonol; Dose Level 5 (4 weeks) : 450mg Antroquinonol; Dose Level 6 (4 weeks) : 600mg Antroquinonol.
A maximum of 36 patients were planned based on a criteria of a maximum of 6 patients per cohort: 1 to 6 patients were planned for each dose group in the accelerated phase; 3 to 6 patients for each dose group in the standard phase .
The method of dose escalation in the accelerated titration phase continued to the next higher dose level until a patient experienced MT or a DLT. Standard titration phase start with 3+3 patients. Dose escalation proceeded sequentially between cohorts.
干预措施: Antroquinonol (Drug)
结局指标
主要结局
To Determind the Maximum Tolerable Dose for Antroquinonol
时间窗: DLT is to be observed during 4 week period
The study design consisted of 2 phases, the accelerated titration phase and the standard titration phase. During the accelerated titration phase, patients were enrolled in a cohort of 1 new patient for each dose level and treated for 4 weeks at that level. Any DLT or instance of MT during any 4 week treatment at any dose level led to the initiation of standard titration (3+3) phase. If none of the first 3 patients experienced any DLT, then dose escalation proceeded for the next cohort of patients. If 1 of 3 patients developed DLT, the cohort was expanded to at most 6 patients (another 3 patients added subsequently). If exactly 1 of the 6 patients experienced DLT, then escalation to the next dose level occurred. If more than 1 patient developed DLT in any dose cohort, the dose escalation was withheld and the prior dose level was considered as the MTD unless the present dose level was level 1
次要结局
- Tmax After Dose(30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1&28)
- Half-life Time From Overall Study(30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1&28)
- Maximum Plasma Concentration After on Day 1(30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1)
- Maximum Plasma Concentration After Dosing on Day 28(30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 28)
- AUC0-t on Day 1(within 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1)
- AUC0-t on Day 28(30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 28)
- Number of Participants in the PP Population With Better Than SD at Target Lesion, Better Than Non-CR/Non-PD at Non-target Lesion and no New Lesion(pre-screening and end of treatment)
- Safety Blood and Urine Test(pre-screenting and every 14-day period)