A Phase I, Multicenter, Open-label, Dose Escalation Study of Intravenous Administration of VCN-01 Oncolytic Adenovirus With or Without Gemcitabine and Abraxane® in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 5
- 主要终点
- Safety and Tolerability by means of Adverse Events (AEs) and laboratory data
研究概览
简要总结
The purpose of this study is to determine the safety and tolerability of VCN-01 either administered alone or in combination with Abraxane®/Gemcitabine, and to determine the recommended phase II dose of VCN-01 alone or in combination with Abraxane®/Gemcitabine.
详细描述
The study consists of three parts:
- Part I is a dose escalation study to determine the safety and tolerability of a single intravenous injection of VCN-01 alone
- In Part II the safety and tolerability of the two highest VCN-01 tolerable doses from part I will be evaluated in combination with Abraxane®/Gemcitabine.
- In Part III the safety and tolerability of the two highest VCN-01 tolerable doses from part I will be evaluated in combination with Abraxane®/Gemcitabine in a "delayed" schedule compared with Part II.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Male/Female patients aged 18 years or over
- •Patients must provide written informed consent
- •Part I: Patients with histologically confirmed, locally advanced or metastatic solid tumors. Part II and Part III: Patients with histologically confirmed, pancreatic adenocarcinoma for which the established therapy is Abraxane®/Gemcitabine (clinical standard of care)
- •Life expectancy above 3 months
- •Patients willing to comply with treatment follow-up
- •ECOG Performance status 0 or 1
- •Adequate baseline organ function (hematologic, liver, renal and nutritional)
- •Use a reliable method of contraception in fertile men and women
排除标准
- •Active infection or other serious illness or autoimmune disease
- •Treatment with live attenuated vaccines in the last three weeks
- •Known chronic liver disease (liver cirrhosis, chronic hepatitis)
- •Treatment with another investigational agent within its five half-lives prior to VCN-01 infusion
- •Viral syndrome diagnosed during the two weeks before inclusion
- •Chronic immunosuppressive therapy
- •Concurrent malignant hematologic or solid disease
- •Pregnancy or lactation. Patients must agree to use effective contraception or be surgically sterile.
- •Patients receiving full-dose anticoagulant / antiplatelet therapy
- •Adequate levels of neutralizing antibodies against adenovirus
- •Patients with Li Fraumeni syndrome or with previous known retinoblastoma protein pathway germinal deficiency
研究组 & 干预措施
Part I: Dose Escalation, Single Agent
Single intravenous injection of VCN-01 oncolytic adenovirus
干预措施: VCN-01 (Genetic)
Part II: Dose Escalation, Combination
Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
干预措施: VCN-01 (Genetic)
Part II: Dose Escalation, Combination
Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
干预措施: Gemcitabine (Drug)
Part II: Dose Escalation, Combination
Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
干预措施: Abraxane® (Drug)
Part III: Dose Escalation, Combination, "delayed" schedule
Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
干预措施: VCN-01 (Genetic)
Part III: Dose Escalation, Combination, "delayed" schedule
Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
干预措施: Gemcitabine (Drug)
Part III: Dose Escalation, Combination, "delayed" schedule
Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
干预措施: Abraxane® (Drug)
结局指标
主要结局
Safety and Tolerability by means of Adverse Events (AEs) and laboratory data
时间窗: At least 6 months
Recommended Phase 2 Dose (RP2D) by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities
时间窗: At least 6 months
次要结局
- Presence of VCN-01 in tumor(Day 8-10)
- Viral Pharmacokinetics(Up to 48 h)
- Viral Shedding(Up to day 28)
- Neutralizing antibodies anti-VCN-01(30 days after end of treatment phase)
- Preliminary anti-tumor activity by Overall Response Rate (ORR)(CT or MRI scans every 8 weeks until disease progression)
- Preliminary anti-tumor activity by Progression Free Survival (PFS)(CT or MRI scans every 8 weeks until disease progression)