Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Neoplasms; Safety and Efficacy (RADNET)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AE) according to CTCA v 4.03, probably or possibly reated to the study drug, reported from the first study-related procedure until 30 days following the last dose, or local injuries caused by the administration procedure checked at each administration of Advince
研究概览
简要总结
The primary objective of this study is to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic NENs and if possible determination of maximum tolerated dose (MTD).
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Subject's written informed consent
- •≥ 18 years of age
- •Must use a reliable method of contraception if sexually active and of reproductive potential
- •Plasma creatinine < 105 µg/ml
- •AST, ALT < 5.0-fold upper limit of normal
- •Total bilirubin < 3.0-fold upper limit of normal
- •PT/INR < 2.0 and PTT within normal limits
- •Neutrophils > 1,500/µl, haemoglobin > 100 g/L, platelets > 100,000/µl
- •Patients with functioning NEN should have cover by somatostatin analog
- •Histologically confirmed NEN of gastrointestinal, pancreatic or bronchial origin
- •Disease progression verified over the last 6 months on CT or MRI using criteria employed in standard practice at the local hospital
- •Disease that is not considered resectable for potential cure or tumor reduction
- •Standard anti-cancer therapy exhausted according to the European Society of Medical Oncology (ESMO) guidelines for GEP-NETs and according to the European Neuroendocrine Tumor Society (ENETS) guidelines for lung carcinoids
- •Adequate liver perfusion ensured e.g. by patent portal vein, patent hepatic veins
- •Liver dominant disease with involvement of < 60% of liver parenchyma
- •Karnofsky performance status of ≥70%
- •Life expectancy of ≥ 6 months
排除标准
- •Known chronic liver dysfunction before the development of metastatic cancer (e.g., cirrhosis, chronic hepatitis)
- •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
- •Active infection, including documented HIV and hepatitis C
- •Any viral syndrome diagnosed within the previous 2 weeks
- •Systemic anti-cancer therapy (except for somatostatin analogues) 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
- •Evidence of clinically significant immunosuppression such as primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
- •Requirement of treatment with corticosteroids (prednisone >10 mg/day or equivalent)
- •Concomitant malignancy
- •Pregnant or lactating females
结局指标
主要结局
Number of Adverse Events (AE) according to CTCA v 4.03, probably or possibly reated to the study drug, reported from the first study-related procedure until 30 days following the last dose, or local injuries caused by the administration procedure checked at each administration of Advince
Number of Adverse Events (AE) according to CTCA v 4.03, probably or possibly reated to the study drug, reported from the first study-related procedure until 30 days following the last dose, or local injuries caused by the administration procedure checked at each administration of Advince
Identify Dose Limiting Toxicity (DLT) from first until last injection of Advince, if possible
Identify Dose Limiting Toxicity (DLT) from first until last injection of Advince, if possible
Changes in laboratory efficacy and safety parameters, biological serum markers and vital signs over time vs baseline values.
Changes in laboratory efficacy and safety parameters, biological serum markers and vital signs over time vs baseline values.
次要结局
- Tumor size and tumor metabolic activity by: a) Computer tomography (CT) and/or positron emission tomography (PET) and/or magnetic resonance imaging (MRI) before first and after last treatment cycle; b) Hormone level screening (biological markers) from baseline until progressive disease; c) Progression-free survival (PFS) 24 weeks after 4th cycle.
- Viral replication by adenovirus quantification of in patients’ blood on day 1, 8, 22 and 50; before and 24h after injection, as well as 72h after injection by QRT-PCR.
- Humoral response by detection of anti-adenovirus neutralizing antibodies at baseline, day 8 and day 50. Cytokine-mediated immune response is determined by cytokine measurement in plasma at baseline, 24h and 72h (optional) following virus injections.
研究者
Department of Immunology, Genetics and Pathology (IGP)
Scientific
Uppsala University