Effectiveness and Safety of Microsurgical Resection Combined With Photodynamic Therapy (PDT) Using Hematoporphyrin Injection (Hiporfin) for Recurrent Glioblastoma: A Prospective, Single-Arm, Open-Label, Single-Center Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Rate of tumor recurrence or progression within 2 years after surgery
研究概览
简要总结
This single-center, prospective, single-arm, open-label clinical study evaluates the effectiveness and safety of microsurgical resection combined with photodynamic therapy (PDT) in patients with recurrent glioblastoma (GBM). Patients receive intravenous hematoporphyrin injection (Hiporfin) 5 mg/kg 48-72 hours before surgery. Standard craniotomy with microsurgical resection of the recurrent tumor is then performed, followed by intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser (fluence 150-200 J/cm2). The primary outcome is the rate of tumor recurrence within 2 years after surgery. Participants are followed postoperatively for up to 24 months with contrast-enhanced brain MRI, neurological and quality-of-life assessments (EORTC QLQ-C30), and adverse event monitoring.
详细描述
Background:
For recurrent glioblastoma (WHO grade IV), no standard therapy has been established, and the median overall survival after recurrence is 24-44 weeks.
Tumor-targeted photodynamic therapy (PDT) uses a photosensitizer that preferentially accumulates in tumor tissue; activation with 630-nm laser light generates reactive oxygen species that selectively kill residual tumor cells while sparing normal brain.
Design:
Prospective, single-arm, open-label, single-center study (Sun Yat-sen University Cancer Center, Guangzhou, China). Planned sample size: 10 participants.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years, any sex
- •KPS score >= 70 and ECOG performance status 0-2
- •Patient and family members willing and able to provide written informed consent
- •Histopathologically confirmed glioblastoma (WHO grade IV) that has progressed or recurred after standard radiotherapy and chemotherapy, based on radiological evidence of measurable disease
- •More than 3 months since completion of brain radiotherapy
- •Hospitalized for recurrence/progression with a sizable lesion causing related symptoms and/or mass effect, for which gross-total or subtotal resection is considered feasible at reoperation
- •No concomitant malignancy, severe autoimmune disease or congenital immunodeficiency, severe active infection, cranial nerve disorder, or psychiatric disease
- •Life expectancy greater than 12 weeks
- •Cardiac function: essentially normal electrocardiogram, stable hemodynamics, left ventricular ejection fraction > 55%
- •White blood cell count > 3.5 x 10^9/L, platelet count > 100 x 10^9/L, absolute neutrophil count > 1.5 x 10^9/L, hemoglobin > 90 g/L
- •ALT and AST < 2.5 x upper limit of normal (< 5 x ULN if hepatic impairment mainly due to tumor infiltration), total bilirubin < 1.5 x ULN, serum creatinine < 1 x ULN
- •INR or prothrombin time < 1.5 x ULN and APTT < 1.5 x ULN (for patients on anticoagulation, PT/PTT within the expected therapeutic range)
- •Negative for HIV antibody, Treponema pallidum antibody, HBsAg, HCV antibody, and EBV-DNA
- •Female subjects must use effective contraception throughout the study, with negative serum or urine pregnancy test at screening and during the study
- •Able to attend regular follow-up visits at the study institution throughout the trial
- •Expected benefit of participation judged to outweigh the risks by the investigators
排除标准
- •KPS score < 70
- •Prior or concurrent malignancy at other sites, unless disease-free for >= 3 years
- •Pregnant or lactating women
- •History of allergy to photosensitizers or hematoporphyrin
- •Porphyria or soy allergy
- •Contraindications to surgery
- •Other uncontrolled active infection
- •Treatment with any investigational drug within 30 days before study entry
- •Psychiatric disease or other conditions (e.g., uncontrolled cardiac or pulmonary disease, diabetes) precluding compliance with study treatment and monitoring
- •Severe renal or hepatic impairment (bilirubin > 1.5 x ULN, alkaline phosphatase and AST > 2.5 x ULN, creatinine clearance < 30 mL/min)
- •Prior allogeneic tissue or organ transplantation
- •Poor compliance or inability to follow skin photosensitivity precautions
- •HIV-positive or AIDS-related disease
- •Contraindications to magnetic resonance imaging
- •Follow-up impossible for psychological, family, social, or geographical reasons
- •Lack of legal capacity (deprived of liberty or under guardianship)
- •Refusal to participate or to provide consent
- •Any other condition judged unsuitable for enrollment by the investigator
研究组 & 干预措施
Microsurgical Resection + PDT
Patients receive hematoporphyrin injection (Hiporfin) 5 mg/kg intravenously in 250 mL normal saline under light protection 48-72 hours before surgery, after a negative skin test. Standard craniotomy with microsurgical resection of recurrent glioblastoma is performed, followed by intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser (1 W, 120-150 mW/cm2, 150-200 J/cm2). Dexamethasone 10 mg IV daily for 3 days preoperatively. Postoperative whole-body light protection for 72 hours and avoidance of direct sunlight for 30 days.
干预措施: Microsurgical Tumor Resection (Procedure)
Microsurgical Resection + PDT
Patients receive hematoporphyrin injection (Hiporfin) 5 mg/kg intravenously in 250 mL normal saline under light protection 48-72 hours before surgery, after a negative skin test. Standard craniotomy with microsurgical resection of recurrent glioblastoma is performed, followed by intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser (1 W, 120-150 mW/cm2, 150-200 J/cm2). Dexamethasone 10 mg IV daily for 3 days preoperatively. Postoperative whole-body light protection for 72 hours and avoidance of direct sunlight for 30 days.
干预措施: Hematoporphyrin Injection (Hiporfin) (Drug)
Microsurgical Resection + PDT
Patients receive hematoporphyrin injection (Hiporfin) 5 mg/kg intravenously in 250 mL normal saline under light protection 48-72 hours before surgery, after a negative skin test. Standard craniotomy with microsurgical resection of recurrent glioblastoma is performed, followed by intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser (1 W, 120-150 mW/cm2, 150-200 J/cm2). Dexamethasone 10 mg IV daily for 3 days preoperatively. Postoperative whole-body light protection for 72 hours and avoidance of direct sunlight for 30 days.
干预措施: 630-nm Semiconductor Laser (Device)
结局指标
主要结局
Rate of tumor recurrence or progression within 2 years after surgery
时间窗: 24 months after surgery (brain MRI every 2 months)
The proportion of participants with radiologically confirmed tumor recurrence or progression on contrast-enhanced brain MRI within 24 months after combined surgery and PDT, assessed according to the radiologic criteria specified in the study protocol (maximum perpendicular diameters of measurable lesions).
次要结局
- Recurrence-free survival (RFS)(From date of surgery (Day 0) to first documented recurrence/progression or last follow-up; MRI every 2 months, up to 24 months)
- Overall survival (OS)(From date of surgery to death from any cause or last follow-up; monthly, up to 24 months)
- Incidence of adverse events, including skin phototoxicity(From study drug administration (Day 0) through Day 360 (+/-1) and all subsequent follow-up visits)
- Change in quality of life (EORTC QLQ-C30)(Baseline (preoperative) through Day 360 (+/-1) and follow-up visits)
研究者
Yonggao Mou
Dr.
Sun Yat-sen University