NCT02449551已完成2 期
Study of AZD6094 (Volitinib) in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Third-line Treatment
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Volitinib is a potent and selective small molecule c-Met kinase inhibitor. Volitinib was found to inhibit c-Met kinase at the enzyme and cell levels with IC50s of 4 nM for both enzyme and Met phosphorylation in the cell. Consistent with its potent enzyme and cell activity, volitinib was found to inhibit cell growth in vitro against tumors with c-Met gene amplification in the absence of HGF stimulation with IC50s generally below 10 nM. It also potently inhibited HGF-stimulated cell proliferation against tumors with c-Met overexpression or carrying a HGF/c-Met autocrine loop.
This study is a single-arm, phase II study of votilinib in patients with advanced gastric adenocarcinoma harboring MET amplification as a third line treatment Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.
To investigate the efficacy of volitinib in patients with advanced gastric adenocarcinoma harboring MET amplification.
详细描述
same as above
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
- •Provision of fully informed consent prior to any study specific procedures.
- •Patients must be ≥20 years of age.
- •Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after second-line therapy.
- •Both fluoropyrimidine and platinum agent need to be contained in the prior chemotherapies
- •Prior adjuvant or neoadjuvant therapy is counted as 1 regimen, provided that disease progression occurs within 6 months after the completion of adjuvant or neoadjuvant therapy.
- •Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Patients with MET amplification.
- •Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- •Eastern Cooperative Oncology Group performance status 0-
- •Patients must have a life expectancy ≥ 3 months from proposed first dose date.
- •Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
- •Haemoglobin ≥9.0 g/dL (transfusion allowed)
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •White blood cells (WBC) > 3 x 109/L
- •Platelet count ≥100 x 109/L (transfusion allowed)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (does not include patients with Glibert's disease)
- •AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
- •Serum creatinine ≤1.5 x institutional ULN
- •At least one measurable lesion that can be accurately assessed by imaging or physical examination at baseline and following up visits.
- •Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day
- •for women of childbearing potential.
- •Provision of consent for mandatory biopsy at progression (fresh frozen will be mandatory if clinically feasible)
- •Provision of archival or fresh tissue sample at baseline (fresh frozen will be mandatory if clinically feasible)
排除标准
- •Are currently enrolled in, or discontinued within the last 21 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
- •Any previous treatment with MET inhibitors
- •Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤5 years.
- •HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
- •Patients unable to swallow orally administered medication.
- •Treatment with any investigational product during the last 21 days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
- •Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
- •With the exception of alopecia, any ongoing toxicities (>Common Toxicity Criteria for Adverse Effects grade 1) caused by previous cancer therapy.
- •Intestinal obstruction or Common Toxicity Criteria for Adverse Effects grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
- •Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- •Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Baseline Left ventricular ejection fraction below the LLN of <55% measured by echocardiography or institution's LLN for MUGA, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
- •Female patients who are breast-feeding or child-bearing and Male or female patients of reproductive potential who are not employing an effective method of contraception
- •Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
- •Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be potent inhibitors of CYP1A2 or CYP3A4, potent inducers of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range.
研究组 & 干预措施
Volitinib
Experimental
Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.
干预措施: Volitinib (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 8 weeks
次要结局
- Duration of response(8 weeks)
- Number of subjects with Adverse Events as a measure of safety and tolerability(8 weeks)
- Objective response rate (ORR)(8 weeks)
- Disease control rate(8 weeks)
- Overall survival (OS)(8 weeks)
研究者
Jeeyun Lee
MD,PhD
Samsung Medical Center
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Study of AZD6094 (Volitinib) in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With MET Overexpression as a Second-line TreatmentAdvanced Gastric AdenocarcinomaNCT02447380Samsung Medical Center2
已完成
1 期
Phase Ib, Single-arm Study of AZD6094 (Volitinib) in Combination With Docetaxel, in Any Solid Cancer and Sequential Phase II, Single-arm Study of AZD6094 (Volitinib) in Combination With Docetaxel in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Second Line TreatmentAdvanced Gastric AdenocarcinomaNCT02447406Samsung Medical Center7
招募中
不适用
Study of Volitinib in advanced gastric adenocarcinoma patients with MET amplification as third-line treatmentKCT0004070Samsung Medical Center15
已完成
不适用
Phase II, single-arm study of AZD6094 (Volitinib) in combination with docetaxel, in advanced gastric adenocarcinoma patients with MET overexpression as a second-line chemotherapyKCT0004048Samsung Medical Center25
进行中（未招募）
不适用
Phase II, single-arm study of AZD6094 (Volitinib) in combination with docetaxel, in advanced gastric adenocarcinoma patients with MET amplification as a second-line chemotherapyKCT0004050Samsung Medical Center25