Phase I Trial of Intraperitoneal Administration of a) a CEA-Expressing Derivative, and b) a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 37
- 试验地点
- 2
- 主要终点
- Dose Limiting Toxicity
研究概览
简要总结
RATIONALE: A gene-modified virus may be able to kill tumor cells without damaging normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of an attenuated oncolytic measles virus therapy and oncolytic virus therapy in treating patients with progressive, recurrent, or refractory ovarian epithelial cancer or primary peritoneal cancer (measles virus vaccine therapy study closed as of 06/02/2008).
详细描述
OBJECTIVES:
- Determine the safety and toxicity of recombinant carcinoembryonic antigen (CEA)-expressing measles virus (MV-CEA) and oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) in patients with progressive, recurrent, or refractory ovarian epithelial or primary peritoneal cavity cancer ( MV-CEA closed as of 06/02/2008).
- Determine the maximum-tolerated dose of MV-CEA and MV-NIS in these patients ( MV-CEA closed as of 06/02/2008).
- Characterize viral gene expression at each dose level as manifested by CEA titers in these patients.
- Assess viremia, viral replication, and measles virus shedding or persistence after study therapy.
- Determine humoral and cellular immune response to the injected virus in these patients.
- Assess, preliminarily, the antitumor efficacy of this therapy, by assessing CA-125 levels, radiographic response, and time to progression, in these patients.
- Determine the time course of viral gene expression and virus elimination and biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography (SPECT/CT) imaging.
- Assess viremia, viral replication, and measles virus shedding/persistence following intraperitoneal administration of MV-NIS.
OUTLINE: This is a dose-escalation study.
Patients receive recombinant carcinoembryonic antigen-expressing measles virus (MV-CEA) or oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) intraperitoneally over 30 minutes on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity ( MV-CEA closed as of 06/02/2008).
Cohorts of 3-6 patients receive escalating doses of MV-CEA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity ( MV-CEA closed as of 06/02/2008).
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 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Dose Limiting Toxicity
时间窗: up to 12 months after last treatment
If one patient experiences a Dose limiting Toxicity(DLT), up to three additional patients will be treated at the same dose level. If DLT is observed in only one of six patients treated at a given dose level, the next cohort of three patients will be treated at the next higher dose level. If two or more patients experience DLT at a particular dose level, then the dose escalation will cease and any subsequent patients will be treated at a lower dose level. Thus finding the Max tolerated dose
次要结局
- Time to Progression(up to 12 months after last treatment)
- Number of Responses (Complete and Partial, Stable and Progressive Disease)(up to 12 months after last treatment)
- Change in CA-125 Levels From Baseline to Last Recorded Value (up to 18 Months)(baseline and up to 18 months)