Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle or Resection Cavity in Children and Adults With Recurrent Posterior Fossa Ependymoma: A Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Number of participants who experienced dose-limiting toxicity (DLT)
研究概览
简要总结
This study seeks to determine the optimum dose frequency of 5-Azacytidin (5-AZA) infusions into the fourth ventricle of the brain. The study's primary objective is to establish the maximum tolerated dose for infusions of 5-Azacytidine into the fourth ventricle in patients with recurrent ependymoma. The study's secondary objective is to assess the antitumor activity of 5-Azacytidine infusions into the fourth ventricle based upon imaging studies and cytology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: Patients with histologically verified ependymoma, with recurrence or progression anywhere in the brain and/or spine. Patients are also eligible if they have refractory disease, which will be defined as residual tumor which has not been completely cleared despite prior treatments. To be eligible, patients' disease must have originated in the posterior fossa of the brain
- •Patient must have either measurable or evaluable tumor as assessed by MRI of the brain and total spine
- •An implanted catheter in the fourth ventricle or posterior fossa tumor cavity attached to a ventricular access device or agreement to have one placed.
- •A minimum of 7 days between last dose of systemic chemotherapy and/or radiation therapy and first infusion of 5-AZA into fourth ventricle
- •Life expectancy of at least 12 weeks in the opinion of the principal investigator
- •Lansky score of 50 or greater if ≤16 years of age or Karnofsky score of 50 or greater if > 16 years of age
- •Existing neurological deficits must have been stable for a minimum of 1 week prior to study enrollment
- •Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
- •Adequate bone marrow function defined by peripheral absolute neutrophil count (ANC) ≥ 500/μL, platelet count ≥ 50,000/μL (transfusion independent), and hemoglobin ≥ 9.0 gm/dL (may receive RBC transfusions)
- •Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
排除标准
- •Enrolled in another treatment protocol
- •Has received another investigational or chemotherapy agent or radiation therapy within 7 days prior to 5-AZA infusion into the fourth ventricle
- •Evidence of untreated infection
- •Pregnant or lactating women
研究组 & 干预措施
group 1
5-Azacytidine (5-AZA) group 1: Enrolled patients will undergo surgical placement of a ventricular catheter into the fourth ventricle that will be attached to a subcutaneously placed reservoir. Patients will be divided into 3 dose groups and receive 8 weeks of intraventricular 5-AZA (12 mg) into the fourth ventricle. Patients in Group 1 will receive two 5-AZA infusions every week.
干预措施: 5-Azacytidine (5-AZA) group 1 (Drug)
group 2
5-Azacytidine (5-AZA) group 2: Enrolled patients will undergo surgical placement of a ventricular catheter into the fourth ventricle that will be attached to a subcutaneously placed reservoir. Patients will be divided into 3 dose groups and receive 8 weeks of intraventricular 5-AZA (12 mg) into the fourth ventricle. Patients in Group 2 will receive three 5-AZA infusions every week.
干预措施: 5-Azacytidine (5-AZA) group 2 (Drug)
group 3
5-Azacytidine (5-AZA) group 3: Enrolled patients will undergo surgical placement of a ventricular catheter into the fourth ventricle that will be attached to a subcutaneously placed reservoir. Patients will be divided into 3 dose groups and receive 8 weeks of intraventricular 5-AZA (12 mg) into the fourth ventricle. Patients in Group 3 will receive four 5-AZA infusions every week.
干预措施: 5-Azacytidine (5-AZA) group 3 (Drug)
结局指标
主要结局
Number of participants who experienced dose-limiting toxicity (DLT)
时间窗: 8 weeks
Dose-limiting toxicity will be defined as any of the following events: New neurological deficit (grade 3 or higher) probably or definitely attributed to intraventricular 5-azacytidine infusions. New adverse event involving any organ probably or definitely attributed to intraventricular 5-azacytidine infusions with the specific exclusion of: Grade 3 or higher nausea and vomiting \< 3 days duration and grade 3 or higher headache \< 3 days duration.
次要结局
- Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)(8 weeks after first infusion)
研究者
David Ilan Sandberg
Professor
The University of Texas Health Science Center, Houston