2025-520814-78-00招募中2 期
FIDES: Focused Ultrasound-mediated Blood-Brain Barrier Opening In Pontine Diffuse Midline Glioma (DMG) to Enhance Systemic Therapy with Temozolomide – an exploratory pilot and feasibility trial
Universitair Medisch Centrum Utrecht2 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2026年3月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Any serious adverse events (SAE) related to the Exablate BBBO device- and procedure, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
研究概览
简要总结
To evaluate the safety of the Exablate-BBBO procedure and device in patients with H3K27-altered pontine DMG receiving TMZ. To determine the 6-month progression-free survival (PFS6) in patients with H3K27-altered pontine DMG treated with Exablate BBBO to TMZ maintenance therapy.
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 4 years.
- •Able to attend all study visits.
- •Able and willing to give informed consent or have a legal guardian who is able and willing to do so.
- •Histologically/molecularly verified de novo pontine H3K27-altered diffuse midline glioma.
- •Main localization (‘center of mass’) in the brainstem. NB: some degree of extension beyond the brainstem, e.g. cerebellar peduncles, is allowed.
- •Karnofsky Performance Score (KPS) or Lansky Performance Score (LPS) of ≥ 70/ KPS or LPS 60 and WHO/ECOG performance status ≤
- •ASA-score of I-III.
- •Intention to treat with (TMZ chemo-) radiation and maintenance TMZ as per consensus of the local multidisciplinary tumor board.
- •Feasible to schedule the first Exablate BBBO procedure preferably within 4-6 weeks, acceptably within 12 weeks, after successful completion of radiotherapy/ concomitant TMZ-chemoradiation, defined as completed treatment as planned without reported CTCAEv6.0 grade 3-4 toxicities or, in case of reported CTCAEv6.0 grade 3-4 toxicities, the toxicities must be resolved to grade 2 prior to inclusion.
- •If on steroids, stable or decreasing dose for at least 7 days prior to inclusion.
排除标准
- •Previous or ongoing participation in other clinical trials with other than standard-of-care tumor-directed treatment(s) for H3K27-altered DMG.
- •Known LVEF < 40 or unstable hemodynamics.
- •Severe hypertension, not adequately controlled with study compatible medication (Adults: RR systolic >180 and/ or RR diastolic >100; Children: >p95 + 12mmHg).
- •History of bleeding disorder and/or coagulopathy.
- •Treatment with anti-coagulant therapy.
- •Severely impaired renal function; creatinine clearance <30 mL/ min.
- •Subjects with significant liver dysfunction; Child Pugh classification C.
- •Known diagnosis of active or untreated hepatitis B, hepatitis C, tuberculosis.
- •Any other illness or medical condition that in the investigator's opinion precludes participation in this study.
- •Pregnant or lactating women.
- •Expected uncontrollable therapy non-compliance/ non-cooperation that is likely to interfere with the study procedure, as per judgement of the investigators.
- •Multifocal or leptomeningeal metastasized disease. Multifocal disease is defined as multiple FLAIR-hyperintense lesions, separated by normal-appearing brain tissue, with or without gadolinium enhancement. Multiple enhancing regions within one continuous FLAIR lesion can be considered as unifocal disease.
- •Head circumference ≤ 49 cm.
- •Weight ≥ 135 kg.
- •Patient ≥ 18 years old, who requires general anesthesia to undergo the Exablate BBBO procedure.
- •Contra-indication for MRI procedures.
- •Known sensitivity to gadolinium-based contrast agents.
- •Known sensitivity to the resonator agent (perflutren; Luminity®/Definity®).
- •Signs/symptoms of elevated intracranial pressure (ICP) (e.g. headache, vomiting, impaired vision/papilledema, impaired consciousness), with corresponding radiographic findings on MRI at time of screening.
- •Severe dysphagia with feeding tube dependency.
- •Evidence of acute clinically significant intracranial hemorrhage. NB: minimal hemorrhagic foci without obvious related clinical symptoms will not serve as grounds for exclusion.
- •Tumor not visible on any pre-therapy or post-radiation imaging.
- •Presence of extracranial / intracranial structures (e.g. metal prostheses, implants, calcifications) on pre-treatment CT-scan/ MRI-scan, significantly interfering with acoustic impedance as per judgement of the researchers.
- •Known co-occurring other malignancy that is progressing or has required active treatment within the past 3 years, with exception of: carcinomas in situ (CIS) and non-melanoma skin cancers.
- •Patients with right-to-left, bi-directional or transient right-to-left cardiac shunts.
研究组 & 干预措施
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide Accord 5 mg hard capsules. (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide Accord 100 mg hard capsules. (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide Accord 180 mg hard capsules. (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide SUN 5 mg hard capsules (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide SUN 100 mg hard capsules (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide SUN 250 mg hard capsules (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide Accord 140 mg hard capsules. (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide Accord 250 mg hard capsules. (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide Accord 20 mg hard capsules. (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide SUN 20 mg hard capsules (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide SUN 180 mg hard capsules (Drug)
Temozolomide Accord 100 mg hard capsules., Temozolomide Accord 180 mg hard capsules., Temozolomide SUN 5 mg hard capsules, Temozolomide Accord 5 mg hard capsules., Temozolomide Accord 20 mg hard capsules., Temozolomide SUN 20 mg hard capsules, Temozolomide SUN 180 mg hard capsules, Temozolomide SUN 100 mg hard capsules, Temozolomide SUN 250 mg hard capsules, Temozolomide Accord 140 mg hard capsules., Temozolomide Accord 250 mg hard capsules., Temozolomide SUN 140 mg hard capsules
Test
干预措施: Temozolomide SUN 140 mg hard capsules (Drug)
结局指标
主要结局
Any serious adverse events (SAE) related to the Exablate BBBO device- and procedure, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
Any serious adverse events (SAE) related to the Exablate BBBO device- and procedure, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
Proportion of patients alive and progression-free at 6 months, based on standardized imaging criteria (e.g., RANO or RAPNO for DMG).
Proportion of patients alive and progression-free at 6 months, based on standardized imaging criteria (e.g., RANO or RAPNO for DMG).
次要结局
- Time from diagnosis to disease progression or death, measured by standardized criteria (e.g., RANO/RAPNO).
- Time from diagnosis to death from any cause.
- Radiological response rate according to the response assessment in neuro-oncology criteria (RANO and RAPNO criteria)
- Extent and consistency of BBB opening as confirmed by T1-weighted contrast-enhanced MRI after each Exablate BBBO session.
- Incidence of adverse events (AE) over time related to the Exablate BBBO device- and procedure, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
研究者
Dr. T.J. Snijders
Scientific
Universitair Medisch Centrum Utrecht
研究点 (2)
Loading locations...
相似试验
尚未招募
不适用
Safety and Efficacy of High-Channel Implanted BCI for Motor Function Improvement in Tetraplegia PatientsTetraplegic Motor Dysfunction Following Brainstem or Spinal Cord InjuryNCT07457645Shanghai Zhongshan Hospital10
招募中
1 期
A Early Study of ABSK131 in Patients With Advanced/Metastatic Solid TumorsNCT07288957Abbisko Therapeutics Co, Ltd266
招募中
1 期
A Phase I/II Study of ABSK141 in Patients With Advanced Solid Tumors ( ABSK141-101 )NCT07417189Abbisko Therapeutics Co, Ltd401
尚未招募
1 期
A Study to Evaluate Efficacy and Safety of HB0043 in Aadult Patients With Moderate to Severe Acne Vulgaris.NCT07449156Shanghai Huaota Biopharmaceutical Co., Ltd.21
尚未招募
不适用
Effects of Ultrasound-Guided Stellate Ganglion Block and Transcutaneous Auricular Vagus Nerve Stimulation on Sleep Quality After Radical Mastectomy for Breast CancerNCT07272954Affiliated Hospital of Jiaxing University136