Clinical Investigation of Sonodynamic Therapy in Conjunction With Chemoradiotherapy for Glioblastoma Management
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Progression - free survival (PFS)
研究概览
简要总结
This Phase II trial tests if sonodynamic therapy (SDT)-a non-invasive treatment using ultrasound to activate a cancer-killing drug-improves outcomes for newly diagnosed glioblastoma patients.
Who? 230 adults (<75 years) with confirmed glioblastoma, adequate organ function, no major health issues.
Groups:
Test Group: SDT + standard therapy (radiation, chemo, bevacizumab). Control Group: Standard therapy alone.
Procedure:
SDT uses the drug Hiporfin® followed by focused ultrasound sessions. Patients avoid sunlight for 1 month.
Study Duration:
Treatment: ~6-8 weeks. Follow-up: 24 months (monthly MRIs).
Key Goal:
Compare progression-free survival (time until tumor worsens) between groups. Secondary goals: overall survival, safety.
详细描述
Detailed Description
This single-center, randomized, open-label Phase II trial evaluates the synergistic efficacy and safety of sonodynamic therapy (SDT) combined with standard chemoradiotherapy in newly diagnosed glioblastoma (GBM). While the Brief Summary outlines the trial's scope, this section elaborates on mechanistic, methodological, and analytical nuances not captured elsewhere.
Scientific Rationale SDT leverages low-intensity, low-frequency focused ultrasound (LILFU) (800 kHz-1 MHz, 1-1.25 W/cm²) to activate the sonosensitizer Hiporfin® (5 mg/kg), generating cytotoxic reactive oxygen species (ROS) selectively within tumor cells. Preclinical data demonstrate SDT disrupts mitochondrial function, enhances DNA damage from temozolomide, and promotes immunogenic cell death. This trial builds on Phase I results (unpublished) showing SDT induced tumor shrinkage in recurrent GBM with minimal toxicity.
Intervention Specifics
SDT Protocol:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form;
- •Age < 75 years;
- •Newly diagnosed postoperative glioblastoma patients pathologically confirmed as glioblastoma;
- •Absence of severe hematopoietic dysfunction or cardiac, pulmonary, hepatic, renal abnormalities, or immunodeficiency. Pre-enrollment laboratory results must meet the following:
- •Hematology:
- •White blood cell count ≥4×10⁹/L
- •Absolute neutrophil count ≥1.5×10⁹/L
- •Platelets ≥100×10⁹/L
- •Hemoglobin ≥90g/L
- •Renal function:
- •Serum creatinine ≤1.2mg/dL or creatinine clearance ≥60mL/min
- •Hepatic function:
- •Total bilirubin ≤1.5×ULN (≤3.0×ULN if liver metastasis present)
- •AST/ALT ≤2.0×ULN (≤5.0×ULN if liver metastasis present)
- •Coagulation:
- •INR ≤2.0, with PT, APTT, and TT within normal ranges;
- •Life expectancy ≥3 months;
- •Adverse reactions from prior anti-tumor therapy recovered to ≤ Grade 1, or complete recovery from surgery (Investigator's judgment);
- •Fertile females and all male subjects must agree to use highly effective contraception (condoms, sponges, gels, diaphragms, IUDs, oral/injectable contraceptives, or implants) during the trial and for 12 months after last Hematoporphyrin use. Fertile females must have negative pregnancy test within ≤7 days before investigational product administration.
排除标准
- •Recurrent glioblastoma, brainstem tumors, or glioblastoma patients having received postoperative chemoradiotherapy;
- •Hypersensitivity to photosensitizers;
- •Uncontrolled infections, refractory epilepsy, and/or intracranial hypertension, and/or hypertension, and/or hyperglycemia;
- •HIV infection, active hepatitis B (HBsAg positive with HBV DNA positive), or hepatitis C (HCV antibody positive);
- •Other malignancies within 5 years without effective control (excluding cervical carcinoma in situ, cutaneous squamous cell carcinoma, or localized basal cell skin cancer);
- •Other Investigator-assessed contraindications for trial participation.
结局指标
主要结局
Progression - free survival (PFS)
时间窗: It is evaluated for up to 5 years from the date of randomization to the date of first documented progression or death from any cause, whichever comes first
次要结局
- Overall survival time(It is evaluated for up to 5 years from the date of randomization to the date of death from any cause.)
研究者
Yingjuan Zheng
Chief physician
The First Affiliated Hospital of Zhengzhou University