An Open Label, Non-randomized Phase 1b Study to Investigate the Safety and Effect of the Oncolytic Virus GL-ONC1 Administered Intravenously Prior to Surgery to Patients With Solid Organ Cancers Undergoing Surgery for Curative-Intent or Palliative Resection
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse events as defined by CTCAE v4.03.
研究概览
简要总结
The purpose of this study is to evaluate the safety of the investigational product GL-ONC1. GL-ONC1, a vaccinia virus, has been genetically modified for use as a potential anti-cancer drug to destroy cancer cells. Vaccinia virus has been used successfully in the past as smallpox vaccine in millions of people worldwide.
详细描述
This is an open-label, non-randomized Phase 1b dose escalation study evaluating the safety and effect of the oncolytic virus GL-ONC1 administered intravenously, with or without eculizumab, prior to surgery in patients with advanced solid organ tumors.
GL-ONC1 is a genetically engineered oncolytic vaccinia virus, which disrupts nonessential genes and expression of the foreign gene expression. Evidence suggest that GL-ONC1 is able to infect tumor tissue and kill tumor cells.
The goals of this study are to evaluate the safety of GL-ONC1 and to assess the pharmacokinetics and pharmacodynamics profile of GL-ONC1 in vivo.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-proven diagnosis of advanced (AJCC, 7th Edition: stage III or IV) or aggressive solid organ cancer.
- •Patients must provide written consent for a core needle biopsy sample of tumor tissue (primary or metastatic).
- •Have evidence of measurable disease (according to RECIST Version 1.1: http:// www.recist.com).
- •Have an ECOG Performance Score of 0 to
- •Have a life expectancy of at least 3 months.
- •Have adequate organ and marrow function
- •Negative serum pregnancy test for females of childbearing potential.
- •Have negative test result for HIV and Hepatitis B or C testing.
- •Have baseline anti-vaccinia antibody titer < 10.
排除标准
- •Current or anticipated use of other investigational agents or marketed anticancer agent while on study (from the time of enrollment through the time of surgery).
- •Patients who have received chemotherapy or radiotherapy within 4 weeks prior to entering the study.
- •Small pox vaccination for 4 weeks before study therapy and during study treatment.
- •Have received prior gene therapy or therapy with cytolytic virus of any type.
- •Have clinically significant cardiac disease
- •Oxygen saturation <90% measured by pulse oximetry at rest.
- •Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study.
- •Have known allergy to ovalbumin or other egg products.
- •Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers)
- •Have a history of allergy to iodinated contrast media.
- •Patients with known brain metastases
- •Pregnant or nursing
结局指标
主要结局
Number of participants with treatment-related adverse events as defined by CTCAE v4.03.
时间窗: 2.5 years
Number of participants with treatment-related adverse events as defined by CTCAE v4.03.
次要结局
- The presence of GL-ONC1 within malignant tumors by examination of the resected surgical specimen.(2.5 years)
- Level of anti-vaccinia neutralizing antibodies in serum(2.5 years)
- Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected tumor tissue(2.5 years)
- The maximum concentration (Cmax) of GL-ONC1 in blood after administration(2.5 years)
研究者
Andrew Lowy
Chief, Division of Surgical Oncology
University of California, San Diego