Fluorescence-Guided Detection of Malignant Gliomas: A Dose Ranging Study Using 5-Aminolevulinic Acid (ALA) Induced Protoporphyrin (PpIX) in a Multicenter Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Assess 2 doses of 5-ALA
研究概览
简要总结
RATIONALE: Imaging procedures that use aminolevulinic acid (ALA) may help find and diagnose residual tumor in participants with grade IV malignant astrocytoma who are undergoing surgery to remove the tumor.
PURPOSE: Our primary long-term goal is to improve the completeness of surgical resection of malignant brain tumor through image- guided fluorescence localization. We hypothesize that the use of qualitative fluorescence imaging and point PpIX concentration quantification will enable more complete tumor resection than normal direct (i.e., white light) visualization, and thereby improve participant survival.
详细描述
OBJECTIVES:
Primary
- Assess 2 doses of 5-ALA, 10kg/mg and 20kg/mg, to determine the optimum ALA dose in terms of both sensitivity and specificity for residual tumor. We will compare residual tumor detection by both in vivo qualitative and quantitative fluorescence imaging using histology of the biopsied tissue as the gold standard.
Secondary
- Assess the correlation between the recorded in vivo qualitative assessment of fluorescence signal from the neurosurgeon with the post-surgical (i.e., ex vivo) absolute PpIX concentration detected both intraoperatively and in ex vivo tissue biopsies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
盲法说明
Neurosurgeons and investigators responsible for determining pathologic characteristics, for quantifying fluorescence images, for extracting chemical PpIX, for co-localizing fluorescence images with MR images will be blinded to the ALA dose and administration time. In case of emergency, such as toxicity or allergic reaction attributable to the drug, the research pharmacist on call will break the blind and inform the physician responsible for clinical management.
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
- •Tumor Pathology: Newly diagnosed or recurrent malignant gliomas WHO grade IV
- •Location: Supratentorial
- •Resection: Tumor must be judged suitable for resection on the basis of imaging studies.
- •Consent: Participants must be able to give written, informed consent as approved by the local IRB
- •Newly Diagnosed Tumors: Participants with newly diagnosed Grade IV glioma who have had not been previously treated with cranial radiation therapy
- •Recurrent Tumors: Participants with recurrent Grade IV gliomas who have failed cranial radiation therapy
排除标准
- •Pregnant women or those who are breast feeding
- •Individuals with history of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis
- •Individuals with history of liver disease in last 12 months
- •Individuals with AST, ALT, ALP, or bilirubin >2.5x normal upper limit any time during the previous 2 months
- •Individuals with plasma creatinine>180 μmol/L
- •Individuals who are unable to comply with photosensitivity precautions
- •Individuals without a grade IV glioma
研究组 & 干预措施
Arm II: Newly diagnosed GBM 20mg/kg
Arm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
干预措施: Surgical Resection (Procedure)
Arm I: Newly diagnosed GBM 10mg/kg
Arm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.
干预措施: aminolevulinic acid (Drug)
Arm I: Newly diagnosed GBM 10mg/kg
Arm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.
干预措施: Surgical Resection (Procedure)
Arm II: Newly diagnosed GBM 20mg/kg
Arm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
干预措施: aminolevulinic acid (Drug)
Arm III: Recurrent GBM 10mg/kg
Arm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.
干预措施: aminolevulinic acid (Drug)
Arm III: Recurrent GBM 10mg/kg
Arm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.
干预措施: Surgical Resection (Procedure)
Arm IV: Recurrent GBM 20mg/kg
Arm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
干预措施: aminolevulinic acid (Drug)
Arm IV: Recurrent GBM 20mg/kg
Arm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
干预措施: Surgical Resection (Procedure)
结局指标
主要结局
Assess 2 doses of 5-ALA
时间窗: 6 hours before midpoint of surgery
This clinical trial has ALA dose at 2 levels (10 and 20 mg/kg) and ALA administration time at 1 time point (6h). During surgery, the intraoperative fluorescence observations and PpIX concentration measurements will be taken by the surgeon. The second part of each biopsy will have the PpIX concentration determined.
次要结局
- Correlation between the amount and location of residual tumor detected intraoperatively by fluorescence imaging and frameless stereotaxy after maximal resection and the post-operative image enhancement on CT scan and/or MRI(Tumor tissue samples are obtained at the same two timepoints (the midpoint of surgery and then after maximal resection of the tumor))
- Correlation between intensity of in vivo fluorescence and the pathologist's quantification of tumor in biopsy specimens (e.g., percentage of tumor present) as measured by PpIX concentration and intra-operative fluorescence intensity(Quantitative fluorescence imaging of tumor tissue and normal tissue at approximately the midpoint of surgery and then after maximal resection of the tumor.)
研究者
Andrew Sloan, MD
Principal Investigator
Case Comprehensive Cancer Center