A Phase I Study of Repeated Neural Stem Cell-Based Virotherapy and Standard Radiation and Chemotherapy for Newly Diagnosed High-Grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity of repeat NSC-CRAd-S-pk7 dosing
研究概览
简要总结
The goal of this clinical trial is to learn about the safety and feasibility of administering repeated doses of neural stem cell (NSC)-conditionally replicative adenovirus (CRAd)-survivin (S)-protomer (p)k7, in persons with newly diagnosed high grade glioma.
The main questions it aims to answer are:
- whether multiple doses of NSC-CRAd-S-pk7 are safe and feasible
- how multiple doses of NSC-CRAd-S-pk7 influence tumor response, overall survival, time to tumor progression, and quality of life.
Participants will:
- undergo a biopsy to confirm high grade glioma, then receive the first dose of NSC-CRAd-S-pk7 into the brain
- about 2 weeks later, undergo surgery to remove the tumor and receive the second dose of NSC-CRAd-S-pk7 into the brain
- start chemoradiation about 2 weeks after surgery, then about 2 weeks later, receive the 3rd dose of NSC-CRAd-S-pk7 into the brain
- four weeks later, at the end of chemoradiation, receive a fourth dose of NSC-CRAd-S-pk7 into the brain.
- after radiation is finished, receive standard of care chemotherapy and tumor-treating fields. Two additional doses of NSC-CRAd-S-pk7 will be given every 4 weeks.
详细描述
The treatment regimen contains 3 phases:
Surgical phase:
Patients undergo a biopsy and upon intraoperative confirmation of high grade glioma, NSC-CRAd-S-pk7 dose #1 will be injected into the biopsy site. Patients will undergo resection of the tumor 14 (+/- 3) days later, administration of second dose of the investigational product (NSC-CRAd-S-pk7 dose #2), and implantation of the catheter system. The investigational product will then be given monthly for a total of 6 doses (see below).
Radiotherapy phase:
After recovery from surgery (usually within 2 weeks), standard chemoradiotherapy will be initiated consisting of daily radiotherapy (2 Gy per fraction x 30 fractions) and concomitant temozolomide (TMZ) chemotherapy (75 mg/m2 daily from day 1 of RT until last day of RT).
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 a high-grade glioma (WHO grade 3 or grade 4).
- •Patients must have presumed high grade glioma (WHO grade 3 or 4) based on clinical and radiologic evaluation for registration.
- •A pathologic confirmation of high grade glioma must be made at the time of stereotactic biopsy prior to NSC-CRAd-S-pk7 injection; if this is not possible, the injection will not be performed and the subject will no longer be eligible for the study).
- •Tumor must be accessible for injection and must not be located in the brainstem or contained within the ventricular system.
- •Planning to undergo standard radiation/chemotherapy.
- •18 years of age or older.
- •Performance status (PS) must be WHO PS of <
- •Stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg/day for the 5 days prior to inclusion
- •Serum glutamic-oxaloacetic transaminase (SGOT or AST) < 3x upper limit of normal
- •Serum creatinine < 2mg/dl
- •Platelets > 100,000/mm3 and white blood cells (WBCs) > 3000/mm3
排除标准
- •Prior or ongoing liver disease including known cirrhosis.
- •Known hepatitis B or C infection, known HIV infection.
- •Chronic use of immunosuppressive drugs (with exception of corticosteroids required for mass effect).
- •Acute viral, bacterial or fungal infections requiring therapy.
- •Pregnant or breast-feeding patients.
- •Evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers).
- •Prior radiation therapy to the brain or prior treatment for brain tumor.
研究组 & 干预措施
NSC-CRAd-S-pk7
NSC-CRAd-S-pk7 1·50 x 10⁸ NSCs loaded with1·875 x viral particles administered intra-tumorally on Day 0 and Day 15, then every 4 weeks for up to 6 total doses.
干预措施: NSC-CRAd-S-pk7 (Biological)
结局指标
主要结局
Dose-limiting toxicity of repeat NSC-CRAd-S-pk7 dosing
时间窗: 8 weeks
Determination of the dose limiting toxicity of repeated dosing of NSC-CRAd-S-pk7
次要结局
- Overall survival(5 years)
- Progression-free survival(18 months)
- Objective response to therapy(5 years)