Phase I Study of Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The purpose of this study is to test the safety of the GL-ONC1 vaccinia virus at different dose levels. The investigators want to find out what effects, good and/or bad, it has on the patient and the malignant pleural effusion. A malignant pleural effusion is a build up of fluid in the chest cavity cause by the cancer.
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
- •Diagnosis of histologically or cytologically documented, malignant pleural effusions (primary non-small-cell lung carcinoma, mesothelioma, and other histologies), who have free pleural space (partial or total) that permits the intrapleural drug instillation. This includes cytologically negative pleural effusion in conjunction with histologically proven malignancy involving the pleura.
- •Age must be ≥ 18 years.
- •All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) Grade ≤
- •Any surgery, where general anesthesia was administered, must have occurred at least 14 days prior to study enrollment.
- •Chemotherapy, radiotherapy or immunotherapy must have stopped more than 7 days prior to receiving study drug; however, small field palliative radiotherapy, TKI therapies and hormonal therapies are allowed.
- •Patients with stage IV malignancy (non-mesothelioma) must have had a brain scan (MRI or CT with contrast) showing no evidence of disease progression within 8 weeks of study enrollment.
- •ECOG Zubrod ≤
- •Required baseline laboratory data include:
- •Absolute neutrophil count (ANC) ≥ 1.5 × 109 [SI units 10^9/L],
- •Platelets ≥ 100 ×10^9 [SI units 10^9/L],
- •Hemoglobin ≥ 9.0 g/dL [SI units gm/L],
- •Serum creatinine ≤ 1.5 × upper limit of normal (ULN),
- •Bilirubin ≤ 1.5 × ULN,
- •AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases)
- •Negative pregnancy test for females of childbearing potential.
排除标准
- •Pregnant or breast-feeding women.
- •Patients with fever or any active systemic infections, including known HIV, hepatitis B or C.
- •Patients on immunosuppressive therapy or with immune system disorders, including autoimmune diseases.
- •Concurrent steroid use of more than an equivalent of 20 mg/day prednisone (or equivalent).
- •Prior splenectomy.
- •Previous organ transplant.
- •Patients with clinically significant dermatological disorders, e.g., eczema or psoriasis, as judged by the principal investigator, or any unhealed skin wounds or ulcers.
- •Clinically significant cardiac disease (New York Heart Association, Class III or IV).
- •Dementia or altered mental status that would prohibit informed consent.
- •Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the principal investigator, would make the patient inappropriate for this study.
- •Known allergy to ovalbumin or other egg products.
- •Prior gene therapy treatments or prior therapy with cytolytic virus of any type.
- •Concurrent therapy with any other investigational anticancer agent.
- •Concurrent antiviral agent active against vaccinia virus (e.g. cidofovir, vaccinia immunoglobulin) during the study.
研究组 & 干预措施
GL-ONC1
This is an open-label, dose-escalating, non-randomized, single-center Phase I therapeutic study of GL-ONC1 originally administered intrapleurally as a single dose and now escalating to three consecutive daily doses in patients with a diagnosis (histologically or cytologically documented) of malignant pleural effusions.
干预措施: GL-ONC1 (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 2 years
MTD is to provide a dosing recommendation for subsequent Phase II studies. Three patients will be enrolled in each cohort at the dose levels shown in the table below in order to determine the Maximum Tolerated Dose (MTD). At the beginning of a new dose level, only one patient will be treated. The first patient in each cohort must be treated and complete 14 days of post-treatment evaluation prior to the treatment of the remaining two patients in that cohort.
次要结局
- evaluation of viral appearance in tumor(2-9 days after intrapleural instillation of virus)
- safety(2 years)
- detection of virus in body fluids(days 2, 3, 4, & 5. pretreatment)
- Therapeutic efficacy(day 60 post treatment (+/-10 days))