Phase I Open Label Ascending Dose Study to Assess the Feasibility and Safety of Intermittent Infusions of MTX110 Administered by Convection-Enhanced Delivery (CED) in Patients With Recurrent Glioblastoma (rGBM) (MAGIC-G1)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Safety of MTX110 administered by CED
研究概览
简要总结
A study designed to assess the safety of MTX110 in patients suffering with recurrent glioblastoma. MTX110 will be administered directly to the site of the tumour via a catheter which is inserted during a surgical procedure at the beginning of the study.
详细描述
A two cohort, ascending dose study of intra-tumoral MTX110 in patients with recurrent glioblastoma. With the aim to assess the safety and also the recommended phase 2 dose of MTX110.
The patient will undergo a surgical procedure to insert a programmable pump and catheter system to allow administration of MTX110 directly to the tumour using Convection Enhanced Delivery (CED).
Cohort A patients will receive one of three potential dose levels of MTX110 as a weekly infusion in order to establish recommended phase 2 dose. This will be based on an accelerated dose titration/3+3 design.
Cohort B patients will follow the 3+3 study design with the starting concentration established in Cohort A. They too will receive MTX110 as a weekly infusion and may undergo catheter repositioning and continued treatment following progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Recurrent glioblastoma.
- •Patients must be healthy enough to tolerate surgery and general anesthesia.
- •Estimated life expectancy of greater than 3 months.
排除标准
- •Patients scheduled to undergo or are undergoing re-irradiation for the recurrent tumour.
- •Patients with a history of glioblastoma treatment with carmustine or Gliadel® wafers.
- •Patients who cannot undergo MRI.
- •Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks, or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week) prior to starting the study drug.
- •Patients may not have received treatment with tumor treating fields ≤ 1 week prior to starting the study drug.
- •Patients may not be less than 12 weeks from completion of radiation therapy for the primary tumor.
- •Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of active; multifocal disease; extensive subependymal disease (tumor touching subependymal space is allowed); tumor crossing the midline or leptomeningeal disease.
- •Posterior fossa location of the tumor, regardless of its morphology.
- •Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin (treatment with tamoxifen or aromatase inhibitors or other hormonal therapy that may be indicated in prevention of prior cancer disease recurrence, are not considered current active treatment).
研究组 & 干预措施
Cohort B: MTX-110 with optional catheter repositioning
Weekly dosing of MTX110 via CED until progression. At progression, optional catheter repositioning may occur, followed by continued weekly dosing of MTX110 until next progression/ unacceptable toxicity.
干预措施: MTX110 (Drug)
Cohort A: MTX-110
Weekly dosing of MTX110 via CED until progression/ unacceptable toxicity.
干预措施: MTX110 (Drug)
Cohort A: MTX-110
Weekly dosing of MTX110 via CED until progression/ unacceptable toxicity.
干预措施: Programmable pump and catheter system (Device)
Cohort B: MTX-110 with optional catheter repositioning
Weekly dosing of MTX110 via CED until progression. At progression, optional catheter repositioning may occur, followed by continued weekly dosing of MTX110 until next progression/ unacceptable toxicity.
干预措施: Programmable pump and catheter system (Device)
结局指标
主要结局
Safety of MTX110 administered by CED
时间窗: Through study completion, an expected average of 28 weeks. DLT period 28 days from first dose.
The frequency and nature of adverse events, serious adverse events and dose limiting toxicities (DLTs).
To determine the recommended Phase 2 dose (RP2D) of MTX110
时间窗: Through study completion, an expected average of 28 weeks
次要结局
- Overall survival(12 months)
- Progression-free survival(6 months)
- Best overall response rate(6 months)