Study of Recombinant Adenovirus (AdVince) in Patients With Neuroendocrine Tumors; Safety and Efficacy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
研究概览
简要总结
An open-labelled, uncontrolled, single-center Phase I/IIa clinical study to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic neuroendocrine tumors (NETs), and if possible determination of maximum tolerated dose.
详细描述
An open-labelled, uncontrolled, single-center Phase I/IIa clinical study to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic neuroendocrine tumors (NETs), and if possible determination of maximum tolerated dose. Secondary objectives include to evaluate the anti-tumoral efficacy of AdVince infusions on metastatic neuroendocrine tumors, to determine the replication profile of AdVince and to determine the humoral (antibody) and cytokine-mediated immune response to AdVince. Minimum 12 and maximum 35 patients will be included, the number is based on the toxicity observed.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject´s written informed consent
- •Histologically and radiologically confirmed progressive neuroendocrine carcinoma of gastrointestinal, pancreatic or bronchial origin with multiple liver metastases. Progression in Clinical symptoms and tumor growth verified over the last 6 months on CT or MRI
- •Cancer that is not considered resectable for potential cure or tumor reduction
- •Patent portal vein and adequate liver perfusion
- •Liver dominant disease with involvement of <60% of liver parenchyma
- •Karnofsky performance status of >=70%
- •Life expectancy of >=6 months
- •>=18 years of age
- •Must use a reliable method of contraception if sexually active and of reproductive potential
- •Plasma creatinine <105 ug/ml
- •Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline Phosphatase (ALP) <3.0-fold upper limit of normal
- •Total bilirubin <2.0-fold upper limit of normal
- •Prothrombin time (PT)/International Normalized Ratio (INR) <2.0 and Prothromboplastin time (PTT) within normal limits
- •Neutrophils >1500/ml, hemoglobin >100 g/L, platelets >100 000/ml
- •Patients with functioning NET should have cover by somatostatin analog
排除标准
- •Known chronic liver dysfunction Before the development of metastatic cancer (e.g. cirrhosis, chronic hepatitis)
- •Active infection, including documented HIV and hepatitis C
- •Any viral syndrome diagnosed within the previous 2 weeks
- •Chemotherapy within the previous 4 weeks Before the first treatment
- •Radiotherapy to the target tumor site within the last 24 weeks from the baseline CT scan
- •Concomitant malignancy
- •Pregnant or lactating females
- •Prior participation in any research protocol that involved administration of adenovirus vectors
- •Treatment with any other investigational therapy within the last 4 weeks, organ transplantation prior to treatment, severe cardiovascular, metabolic or pulmonary disease
- •Continuing treatment with any other cancer therapy
研究组 & 干预措施
AdVince
Dose escalation, minimum 3 patients per dose in Phase I. Dose levels:
- 10 000 000 000 virus particles
- 100 000 000 000 virus particles
- 300 000 000 000 virus particles
- 1000 000 000 000 virus particles
Maximum tolerated dose will be confirmed by 12 additional patients treated at this dose level in Phase IIa.
干预措施: AdVince (Drug)
结局指标
主要结局
Number of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
时间窗: From screening visit and through study completion, an average time of 18 months.
AEs probably or possibly related to the study drug or local injuries caused by the administration procedure. If possible identify dose limiting toxicity (DLT), i.e. grade 4 toxicity of any duration or grade 3 toxicity lasting more than 7 days, excluding flu-like symptoms, according to CTCAE v4.03.Clinically significant changes in laboratory parameters (haematology, blood coagulation, liver function, biochemistry and kidney function) and vital signs (body temperature, heart rate, blood pressure, respiratory rate and consciousness according to Reaction Level Scale from 1985 (RLS-85).
次要结局
- Change in tumor size(Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2))
- Change in tumor metabolic activity(Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2))
- Progression-free survival (PFS)(Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.)
- Change in replication profile of AdVince(Before and 72hrs after each treatment cycle up to a time period of 214 days.)
- Change in the humoral immune response to AdVince(At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days.)
- Change in the cytokine-mediated immune response(At baseline and at 72hrs following each treatment up to a time period of 214 days.)