A Phase I Safety and Window-of-opportunity Study of Preoperative Intratumoral Injection of OX40-ligand Expressing Oncolytic Adenovirus (DNX-2440) in Patients With Resectable Liver Metastasis
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) achieved during dose-escalation phase
研究概览
简要总结
The purpose of this study is to test an experimental oncolytic adenovirus called DNX-2440 in patients with resectable multifocal (≥ 2 lesions) liver metastasis, who are scheduled to have curative-intent liver resection surgery. Up to 18 patients will receive two sequential intra-tumoral injections of DNX-2440 into a metastatic liver tumor prior to surgery for liver resection, to evaluate safety and biological endpoints across 3 dose levels (dose escalation). Upon conclusion of the dose-escalation phase, the selected safe and biologically appropriate dose will be administered using the same schema for an additional 12 patients with colorectal cancer liver metastasis (expansion cohort) using established biologic endpoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 or female aged ≥ 18 years at time of consent
- •Diagnosis of liver metastases from colorectal, breast, gastric, periampullary, melanoma, renal cell cancer, sarcoma, squamous cell carcinoma or gastrointestinal stromal tumor
- •Multiple (≥ 2) liver tumors
- •Candidate for curative-intent surgery
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Candidates eligible for targeted therapy, as per standard of care guidelines (and based on mutational status as indicated), must have completed therapy
- •Preoperative chemotherapy is allowed
排除标准
- •Recurrence of liver metastasis
- •Diagnosis of neuroendocrine tumor liver metastasis
- •Liver metastasis treated with > 12 cycles of systemic chemotherapy
- •Condition that requires ongoing systemic immunosuppressive therapy
- •Evidence of inadequate organ function based on lab parameters
- •Liver transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) or total bilirubin > 5x the upper limits of normal
- •Males or females who refuse to use a double-barrier form of birth control during the study and for up to 6 months after injection with DNX-2440
结局指标
主要结局
Maximum tolerated dose (MTD) achieved during dose-escalation phase
时间窗: 1.5 Years
The MTD will be defined as the highest tolerated dose below the dose that results in greater than or equal to one-third of the subjects exposed who experience a dose-limiting toxicity (DLT).
次要结局
- Efficacy of DNX-2440 assessed by Tumor Regression Grade (TRG) score(3 Years)
- Measure Immune response with ImmunoSEQsec(3 Years)
- Measure Immune response with cell response panels(3 Years)
- Viral replication(3 Years)
- Measure Immune response with ELISPOT(3 Years)