Phase 1/2a Study to Determine the Safety of Intratumoral Infusion of Large Surface Area Microparticle (LSAM)-Cisplatin in Participants With Diffuse Midline Glioma (DMG), Including Diffuse Intrinsic Pontine Glioma (DIPG)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 主要终点
- Number of Subjects With Treatment Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
Open-label, dose-escalating, Phase 1/2a trial of Large Surface Area Microparticle (LSAM)-Cisplatin to treat participants with diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), via stereotactic infusion under intraoperative magnetic resonance imaging (MRI) guidance.
详细描述
Large Surface Area Microparticle (LSAM)-Cisplatin consists of large surface area microparticles of the chemotherapy drug cisplatin. These microparticles are administered as a single-magnetic resonance imaging (MRI) guided infusion directly into the tumor to target cancer at the site of the disease with less systemic exposure than intravenously administered chemotherapy. In this study, all participants with diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), will receive LSAM-Cisplatin and will be evaluated to determine whether it is safe and has an effect on the tumor.
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
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 3 to ≤ 21 years.
- •Diagnosis of diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), based on characteristic magnetic resonance imaging (MRI) findings and/or histopathologic confirmation.
- •Prior radiation treatment must have included focal radiation therapy per institutional standard of care and must have been initiated within 6 weeks of diagnosis.
- •At least 4 weeks, but no more than 12 weeks, post-completion of radiotherapy treatment.
- •A standard of care post-radiation magnetic resonance imaging (MRI) performed 4 to 6 weeks after radiation therapy is required for confirmation of eligibility.
- •Performance status [Karnofsky Performance Scale or Lansky Performance Score] within 14 days of Day 1 ≥
- •Absence of other significant medical condition.
- •A legal parent/guardian and/or participant must be able to understand and be willing to sign a written informed consent and/or assent document, as appropriate.
排除标准
- •Untreated symptomatic hydrocephalus at the time of consent, has metastatic or disseminated disease, or leptomeningeal disease.
- •Magnetic resonance imaging (MRI) findings that preclude stereotactic procedure.
- •Intercurrent illnesses or conditions which preclude participation: active systemic infections, autoimmune disease requiring systemic immunomodulation, active or uncontrolled seizure disorder, central nervous system (CNS) vasculopathy or aneurysms, Grade ≥3 cardiac dysfunction, Fridericia-corrected QT interval (QTcF) ≥470 ms.
- •Abnormal organ function:
- •Renal insufficiency: glomerular filtration rate (GFR) ≤ 60 mL/min/1.73m² (with Schwartz equation)
- •Hepatic dysfunction: aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN) and 3 x upper limit of normal (ULN) in the presence of liver metastases; or bilirubin ≤ 1.5 x upper limit of normal (ULN) and 3 x upper limit of normal (ULN) in the presence of Gilbert disease
- •Bone marrow suppression:
- •absolute neutrophil count (ANC) < 1,000/μL
- •platelets < 100,000/μL
- •Coagulopathy or international normalized ratio (INR) > 1.5
- •Receiving any anticoagulants or antiplatelet drugs; any drugs known to cause ototoxicity and nephrotoxicity; receiving any other tumor-directed therapy.
- •Known allergy or hypersensitivity to the study agent (including cisplatin and diluent components).
- •Female participants of childbearing potential must not be pregnant or breast-feeding.
研究组 & 干预措施
LSAM-Cisplatin 6 mg/mL
Phase 1 (Dose Escalation): Intratumoral infusion of LSAM-Cisplatin 6 mg/mL using sequential, dose escalating cohorts.
Phase 2 (Dose Expansion): Intratumoral infusion of LSAM-Cisplatin 6 mg/mL at the recommended Phase 2 dose (RP2D).
干预措施: LSAM-Cisplatin (Drug)
结局指标
主要结局
Number of Subjects With Treatment Emergent Adverse Events (Safety and Tolerability)
时间窗: Day 1 to Week 24
Treatment Emergent Adverse Events will be assessed by changes in adverse events, changes in concomitant medications, changes in laboratory values, and physical exams.
Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability)
时间窗: Day 1 to Week 24
Treatment Emergent Adverse Events will be assessed by changes in adverse events, changes in concomitant medications, changes in laboratory values, and physical exams.
次要结局
- Overall Survival (OS)(Day 1 to Week 24)
- Concentration of Cisplatin in the Systemic Circulation Post-infusion(Day 1 to Week 8)
- Objective Response Rate (ORR)(Weeks 4, 12, and 24)
- Progression-Free Survival (PFS)(Day 1 to Week 24)
- Concentration of Cisplatin in the Cerebrospinal Fluid (CSF) Post-infusion(Prior to infusion to Week 24)