ASCO2013:一线治疗之Nintedanib对索拉非尼的头对头临床试验
Nintedanib是一个口服的酪氨酸激酶抑制剂,靶点包括VEGF、PDGF和FGF信号通路。在这个2期临床研究中,患者按照2:1的比例随机接受nintedanib或索拉非尼治疗,预期2013年年底可以获得研究结果。
摘要详情:
Abstract:
Background: While sorafenib is established as the standard first-line treatment for patients with advanced HCC, its use can be complicated by the occurrence of drug-related adverse events (AEs). Nintedanib, a potent, oral triple angiokinase inhibitor that targets VEGF, PDGF and FGF signaling (as well as Flt3 and RET), has demonstrated clinical activity in various advanced solid tumors with a relatively low incidence of AEs typically associated with angiogenesis inhibitors (e.g. skin toxicity, hypertension, hemorrhage, and hematologic toxicity) and is currently in phase III for non-small cell lung cancer and ovarian cancer. In the Phase I, dose-finding stage of this ongoing, multicenter, open-label Phase I/II trial (NCT01004003), 200mg twice daily (bid) was established as the maximum tolerated dose of nintedanib in previously untreated patients with advanced HCC (Palmer D, et al. Ann Oncol 2012;23(Suppl 9):ix245[Abs 740P]). Nintedanib had an acceptable liver AE profile; the most common AEs were mild/moderate gastrointestinal toxicities.
Methods: The randomized Phase II stage of the trial aims to assess the efficacy, safety, and pharmacokinetics of nintedanib in comparison with sorafenib. Eligible patients have pathologically confirmed, measurable HCC that is not amenable to local therapy, ECOG Performance Status of ≤2, Child-Pugh score of 5–6 (Class A), AST/ALT levels ≤2× upper limit of normal, and no prior systemic therapy. Patients are being stratified by macrovascular invasion and/or extrahepatic spread and then randomized 2:1 to receive nintedanib 200mg bid or sorafenib 400mg bid in continuous 28-day cycles until progression or unacceptable toxicity. Overall, 93 patients were randomized between Sept 2011 and Nov 2012. The primary endpoint is time to progression (TTP) by independent review, according to RECIST 1.0. TTP will be estimated in the treated set by Kaplan–Meier methodology with treatment effects compared using a Cox proportional hazards model. Secondary endpoints include overall survival, tumor response, progression-free survival, safety and pharmacokinetics. Results are due late 2013.
Clinical trial information: NCT01004003.
- ASCO2013:复旦大学附属肿瘤医院杜祥教授发现新型生物标记物可用于弥漫大B细胞淋巴瘤分子分型及预后
- ASCO2013:一线治疗之Nintedanib对索拉非尼的头对头临床试验
- ASCO2013:二线治疗之Regorafenib的三期临床试验
- ASCO2013:一线治疗之索拉非尼上市后的临床监测
- ASCO2013:流行病学之性别对肝癌患者生存的关系
- ASCO2013:流行病学之糖尿病是罹患肝癌的独立危险因素
- ASCO2013:观察性研究之乙肝相关肝癌和丙肝相关肝癌的VEGF通路相关分子的表达对比
- ASCO2013:标志物之VEGF及VEGFR的基因多态性与索拉非尼治疗毒性及疗效的相关
- ASCO2013:二线治疗之PF-03446962 (ALK-1单抗)的1期临床研究
- ASCO2013:一线/二线治疗之TGF-β抑制剂(LY2157299)