Pilot Study for the Use of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency: A Phase I Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Safety of using navigated focused ultrasound (NaviFUS) CTCAE v6.0
研究概览
简要总结
Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency.
详细描述
In this phase I clinical trial, 6-8 patients with recurrent glioblastoma and identified mismatch repair (MMR) deficiency will be administered pembrolizumab along with focused ultrasound sonication following surgery for recurrent glioblastoma. Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first. The primary endpoint will be safety and tolerability, with secondary efficacy endpoints and exploratory biomarker and radiographic analyses
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
- •Patient previously diagnosed with WHO grade 4 IDH-wildtype GBM, determined through genomic and/or histopathological analysis.
- •Prior treatment for GBM with surgical resection and standard of care TMZ and radiation therapy.
- •Patient who has undergone repeat surgery (including biopsy or resection) for rGBM.
- •MMR deficiencies confirmed per standard of care immunohistochemical analysis or Next Generation Sequencing (NGS) of the patient's surgical sample from the time of initial GBM diagnosis or recurrence.
- •Area of sonication using the NaviFUS platform is >30 mm from the skull surface, assessed on the Investigator's review of the screening MRI.
- •Age ≥18 years.
- •Karnofsky Performance Scale (KPS) >
- •Adequate organ and marrow function:
- •Leukocytes ≥2,500/mm3 Absolute Neutrophil Count ≥1,500/mm3 Absolute Lymphocyte Count ≥800/mm3 Platelets ≥100,000/mm3 Hemoglobin ≥8 g/dL
- •Negative serum or urine pregnancy test in a female patient of childbearing potential.
- •Patient or a legally-authorized representative must provide study-specific informed consent.
排除标准
- •Multifocal or leptomeningeal disease observed at the time of GBM recurrence.
- •Patient for whom the repeat surgical cavity is ≤30 mm from the skull surface or otherwise not reasonably accessible for sonification using the NaviFUS platform, assessed on screening MRI.
- •Patient with a prior or concurrent malignancy that is deemed to be clinically significant in the context of rGBM.
- •Patient receiving concurrent treatment with an immune checkpoint inhibitor, other investigational agent, or live vaccine administered within 14 days prior to the first dose of trial treatment.
- •Prior treatment with an immune checkpoint inhibitor agent.
- •Period of less than 28 days from the time of the patient's receipt of other systemic anti-cancer therapies to the proposed date of first trial treatment.
- •Treatment with systemic corticosteroids at an increased dose or dose of ≥10 mg of prednisone (or equivalent) daily within the 5 days prior to starting trial treatment, or treatment with systemic corticosteroids for other indications.
- •Patient with a history of organ transplant or autoimmune disorder requiring active immunosuppression.
- •Patient with current recreational drug use or a history of substance use disorder.
- •Patient with an active concurrent comorbidity that, in the opinion of the Investigator, would pose a safety concern for the patient's participation in this clinical trial.
研究组 & 干预措施
Pembrolizumab + focused ultrasound sonication
Pembrolizumab along with focused ultrasound sonication following surgery for recurrent glioblastoma. Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first. The primary endpoint will be safety and tolerability, with secondary efficacy endpoints and exploratory biomarker and radiographic analyses.
干预措施: Pembrolizumab (Drug)
Pembrolizumab + focused ultrasound sonication
Pembrolizumab along with focused ultrasound sonication following surgery for recurrent glioblastoma. Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first. The primary endpoint will be safety and tolerability, with secondary efficacy endpoints and exploratory biomarker and radiographic analyses.
干预措施: Navifus Focused Ultrasound Sonification (Device)
结局指标
主要结局
Safety of using navigated focused ultrasound (NaviFUS) CTCAE v6.0
时间窗: Assessed at each study visit from baseline through 2 years.
To evaluate the safety of using navigated focused ultrasound (NaviFUS) combined with pembrolizumab (PEM) after repeat surgery for patients with recurrent glioblastoma (rGBM) and mismatch repair (MMR) deficiency. Given that NaviFUS and PEM have defined intracranial dosing, no dose-escalation scheme will be employed. A CTCAE v6.0 grade 4 or higher toxicity probably or definitely attributable (see Section 13.2.3) to the administration of NaviFUS or PEM will be used as the definition for unacceptable toxicity
Feasibility of using navigated focused ultrasound (NaviFUS) -CTCAE v6.0 criteria
时间窗: Assessed at each study visit from baseline through 2 years.
To evaluate feasibility of using navigated focused ultrasound (NaviFUS) combined with pembrolizumab (PEM) after repeat surgery for patients with recurrent glioblastoma (rGBM) and mismatch repair (MMR) deficiency. Given that NaviFUS and PEM have defined intracranial dosing, no dose-escalation scheme will be employed. A CTCAE v6.0 grade 4 or higher toxicity probably or definitely attributable (see Section 13.2.3) to the administration of NaviFUS or PEM will be used as the definition for unacceptable toxicity
次要结局
- Overall survival- standard Kaplan-Meier method and calculated from the date of GBM diagnosis(Baseline through 2 years)
- Progression free survival - standard Kaplan-Meier method and calculated from the date of GBM diagnosis(Baseline through 2 years)
研究者
Jennifer Leddon
Principal Investigator
University of Cincinnati