An Open-Label Phase 2 Study of Surufatinib in Patients With Neuroendocrine Tumours in Europe
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Hutchmed
- 入组人数
- 78
- 试验地点
- 23
- 主要终点
- Disease Control Rate (DCR)
研究概览
简要总结
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs).
详细描述
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated NETs.
The study will enroll 4 cohorts of varying NETs, as follows:
- Cohort A - NET of lung origin
- Cohort B - NET of small bowel origin
- Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin
- Cohort D - NET of any origin (DDI substudy)
All patients will be treated with oral surufatinib 300 mg QD in treatment cycles of 28 days starting on Cycle 1 Day 1.
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
- •Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies;
- •Has radiologic evidence of progressive tumour within 12 months of study enrolment
- •Is willing and able to provide informed consent
- •Is ≥18 years of age
- •Has measurable lesions according to RECIST Version 1.1
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception
排除标准
- •Has an AE due to previous anti-tumour therapy that has not recovered to ≤CTCAE Grade 1, except alopecia and peripheral neurotoxicity with ≤CTCAE Grade 2 caused by platinum chemotherapy
- •Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment.
- •Prior VEGF/VEGFR-targeted therapy
- •Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication
- •Gastrointestinal disease or condition within 6 months prior to first dose
- •Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks) within 6 months of first dose of study drug.
- •Clinically significant cardiovascular disease.
- •Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease (SD) for 14 days or longer; patients requiring steroids within 4 weeks prior to start of study treatment will be excluded.
- •A high risk of bleeding at screening due to tumour invasion into major vessels, such as pulmonary artery, the superior vena cava, or the inferior vena cava, as determined by investigators.
- •Has arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic events (including stroke and/or transient ischaemic attack) within 12 months.
- •Has a clinically meaningful ongoing infection (eg, requiring intravenous treatment with anti-infective therapy)
研究组 & 干预措施
Surufatinib
Cohorts A, B, and C: oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1
Cohort D:
Surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day and single doses of drug cocktail on Day-2 and Day 15 Cycle 1
干预措施: Surufatinib (Drug)
结局指标
主要结局
Disease Control Rate (DCR)
时间窗: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
The DCR was defined as the percentage of patients who achieved a best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study.
次要结局
- Plasma Concentrations of Surufatinib(Cohorts A, B and C: Pre-dose and 1, 2, 3, 4 hours post-dose on Cycle 1 Day 15; Cohort D: Pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8 and 10 hours post-dose on Cycle 1 Day 15)
- Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment(From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months)
- Objective Response Rate (ORR)(RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months)
- Time to Response (TTR)(RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months)
- Duration of Response (DOR)(RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months)
- Progression-Free Survival (PFS)(RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months)
- Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline(Baseline (Day -2) and Cycle 1 Day 15)
- Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months)