NCT03389815Unknown1 期
The Dose-escalation Study Followed by an Extension Phase Evaluating the Safety, Pharmacokinetics and Efficacy of WX-0593 in Advanced Solid Tumor Patients With Anaplastic Lymphoma Kinase（ALK）/Receptor Tyrosine Kinase（ROS1） Positive
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose（MTD）
研究概览
简要总结
The purpose of the study is to evaluate safety, pharmacokinetics and efficacy of WX-0593 alone in the treatment of advanced cancer.
详细描述
The first part is a single-arm, phase 1, open label, dose-escalation design in patients with anaplastic lymphoma kinase（ALK）/receptor tyrosine kinase（ROS1） Positive ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in anaplastic lymphoma kinase(ALK) expression.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 to 70 years, inclusive.
- •Female or male
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Life expectancy of at least 12 weeks.
- •At least one measurable lesion (according to RECIST v1.1)
- •Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy with ALK/ROS1+ (For the expansion phase, patients must have NSCLC with ALK+ ):
- •Patients with advanced tumor (eg. NSCLC, lymphoma, inflammatory myofibroblastic tumor) who failed in standard treatment (eg. resistant of ALK inhibitors or chemotherapy)
- •Patients with advanced NSCLC who cannot accept chemotherapy or intolerance with chemotherapy.
- •Advanced NSCLC patients who could not afford ALK inhibitor treatment.
- •Patients with treated or untreated asymptomatic Central Nervous System（CNS） metastases may be allowed to enroll.
- •Patients must have normal function as defined: ANC≥1.5*10^9/L PLT≥100*10^9/L， Total Bilirubin （TBIL）≤1.5*Upper Limit of Normal（ULN） ( Gilbert's Syndrome TBIL ≤3.0*ULN and DBIL≤1.5*ULN )，Alanine Transaminase （ALT）and Aspartate Aminotransferase（AST）≤2.5*ULN. For liver metastasis patients, ALT and AST≤5*ULN, Cr≤1.5*ULN, LVEF≥50%.
- •Any surgery or radiation (expect for palliative radiation) must have been completed at least 4 weeks prior to first dosing. Palliative radiation must have been completed at least 48 hours prior to first dosing.
- •All related adverse events from previous anti-cancer therapies must have recovered to ≤ Grade 1 (except for alopecia).
- •Patients must be able to understand and volunteer to sign the informed consent.
排除标准
- •Clinically significant cardiovascular disease within 3 months prior to first dosing.
- •Ongoing cardiac dysrhythmias, or any grade of uncontrolled atrial fibrillation, or prolonged QT interval (QTc > 480 ms).
- •Patients need medications that may prolong QT interval or induce torsades de pointes within 14 days prior to the first dosing or during the study.
- •Peripheral neuropathy ≥ Grade 3 according to CTCAE 4.
- •Patients who received continuous use of steroids for more than 30 days, or who need long-term use of steroid hormones or other immunosuppressive agents.
- •History of extensive disseminated/bilateral pulmonary interstitial fibrosis, interstitial fibrosis or interstitial lung disease of Grade 3/4 .
- •Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of WX-
- •Patients who are receiving warfarin sodium (Coumadin) or any other coumadin-derived anticoagulants，and patients with coagulation disturbance and bleeding tendency.
- •Patient has received other investigational drug within 1 month.
- •Patients with acute or chronic infectious medical conditions, including active hepatitis (Hepatitis A、 Hepatitis B、 Hepatitis C ) or HIV infection.
- •Patients who received prior anti-cancer therapy within 2 weeks (t1/2 ≤ 3 days) or within 4 weeks (3 days < t1/2）. Patients previously treated with crizotinib could start WX-0593 dosing after 1 week from the last dosing.
- •Patients who could not discontinue therapy with potent CYP3A4 inhibitors or inducers within 1 week prior first dosing, or patients who need therapy with CYP3A4 inhibitors or inducers during the study.
- •Patients received medications known to be metabolized by CYP3A4 and with narrow therapeutic indices, who could not discontinue within 1 week prior to the start of WX-0593 administration. Patients who need therapy with those medications during the study.
- •Females who are pregnant or breastfeeding.
- •Patients with childbearing potential must agree to use adequate contraception for the duration of treatment and for 6 months after the study.
- •Drug abusers and alcoholics.
- •History of definite nerves or psychosis diseases including epilepsy or dementia.
- •History of other malignancy.
- •Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled.
研究组 & 干预措施
WX-0593 Tablets
Experimental
The first part is a dose-escalation design in patients with ALK/ROS1-positive solid tumor. The second part is an expansion in non-small cell lung Cancer (NSCLC) characterized by abnormalities in ALK expression.
干预措施: WX-0593 Tablets (Drug)
结局指标
主要结局
Maximum tolerated dose（MTD）
时间窗: 28 days
The MTD is determined by the number of the participants in cohort who suffer a dose-limiting toxicity (DLT). The MTD is defined as the former dose at which more than one third of the participants develop a DLT. If no DLTs are observed, the MTD is not reached.
次要结局
- Tmax of WX-0593(28 days)
- Cmax of WX-0593(28 days)
- Cmin of WX-0593(28 days)
- AUC of WX-0593(28 days)
- tl/2 of WX-0593(28 days)
- Cssmin of WX-0593(28 days)
- AUCss of WX-0593(28 days)
- DF of WX-0593(28 days)
- Cssmax of WX-0593(28 days)
- Css-av of WX-0593(28 days)
- CLs of WX-0593(28 days)
- Disease Control Rate (DCR)(From fist administration of WX-0593 to 28 days after last medication.)
- Vz of WX-0593(28 days)
- Progression-free survival (PFS)(From fist administration of WX-0593 to 28 days after last medication.)
- Duration of Response (DOR) and so on(From fist administration of WX-0593 to 28 days after last medication.)
- Objective Response Rate (ORR)(From fist administration of WX-0593 to 28 days after last medication.)
研究者
研究点 (1)
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