A Prospective, Multicentre, Open-label, Randomised Phase 2 Trial to Study the Efficacy and Safety of Anlotinib Hydrochloride Versus Imatinib Mesylate in Locally Advanced, Unresectable or Metastatic Chordoma
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Objective response rate, ORR
研究概览
简要总结
For local relapse not amenable to reasonable curative surgery or for those with metastatic chordoma, chemotherapy is recognised as inactive. The major study drug is the small molecular tyrosine kinase inhibitors targeted at the stem cell factor receptor (KIT) and the platelet-derived growth factor receptors (PDGFRA and PDGFRB), eg. imatinib. Anlotinib is a novel tyrosine kinase inhibitor targeting both at VEGFR-2, -3 and PDGFRA and PDGFRB with high affinity, which also showed broad antitumor activity against EGFR and so on. Thus this multicenter, two-armed phase II trial of PKUPH-sarcoma 05 intended to investigate the efficacy and safety of anlotinib versus imatinib on advanced chordoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 years and older;
- •histologically proven metastatic or locally advanced chordoma, reviewed by the Pathology Committee of Peking University People's Hospital;
- •not amenable to curative-intent surgery;
- •measurable with computed tomography scan or magnetic resonance imaging, per RECIST, version 1.1.
排除标准
- •Eastern Cooperative Oncology Group (ECOG)30 performance status more than 2 ;
- •life expectancy less than 12 weeks;
- •with severe or uncontrolled medical disorders (≥grade 2 of Common Terminology Criteria for Adverse Events version 4.03 [CTCAE version 4.03]) that could jeopardise the outcomes of the study, for example, cardiac clinical symptom or disease with LVEF (left ventricular ejection fraction) <50%, hypertension that could not be well controlled through antihypertensive drugs and so on;
- •weight loss of 20% or more before illness;
- •brain or leptomeningeal metastasis;
- •surgical procedure or radiotherapy within 4 weeks of enrollment;
- •active gastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
- •proteinuria or hematuria;
- •denutrition with albuminemia less than 25 g/L;
- •pregnant or breastfeeding status;
- •other malignancy, positive HBV/HCV/HIV serology;
- •known allergy to the experimental agents;
- •had ever used anti-angiogenesis TKIs.
研究组 & 干预措施
Arm A: anlotinib arm
anlotinib was given at a fixed dose of 12mg D1-14 every 21 days
干预措施: Anlotinib Hydrochloride (Drug)
Arm B: imatinib arm
Imatinib was given at dose of 400 mg twice daily continuously
干预措施: Anlotinib Hydrochloride (Drug)
结局指标
主要结局
Objective response rate, ORR
时间窗: 6 months
CR+PR in the intent-to-treat population according to RECIST, version 1.1
Progression-free Survival, PFS
时间窗: 2 years
Progression-free survival is defined as time from randomisation to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment or randomisation
次要结局
- Overall Survival, OS(5 years)