Clinical Safety Study on 5-Aminolevulinic Acid (5-ALA) in Children and Adolescents With Brain Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 7
- 主要终点
- Safety of 5-ALA for fluorescence-guided resections in children and adolescents determined as incidence of adverse events of CTCAE grade III-V.
研究概览
简要总结
In this prospective, open, single-armed, multicenter, phase II study for application of 5-ALA in children and adolescents with brain tumors 80 patients will be investigated.
Primary objective of the study is to determine the safety of 5-ALA for fluorescence-guided resections in children and adolescents with intra-axial brain tumors.
Secondary objectives are
- to determine whether fluorescent tissue truly signifies tumor (positive predictive value) in various pediatric brain tumors
- to determine the degree of tumor resection on early post-operative MRI
- and to determine the pharmacokinetics of 5-ALA in this population.
详细描述
In 2007, 5-aminolevulinic acid (5-ALA) was approved in Europe by the European Medicines Agency (EMA) (brand name: Gliolan®) for "the visualization of malignant tissue during surgery for malignant glioma (WHO III and IV) in adults." Similarly, approval for 5-ALA was granted by the FDA in 2017 as an "optical imaging agent indicated in patients with gliomas (suspected World Health Organization Grades III or IV on preoperative imaging) as an adjunct for the visualization of malignant tissue during surgery" (brand name: Gliolan®). Goal of the study is to investigate if the use of 5-ALA is safe in children and get preliminary information on the type of paediatric brain tumors which are suitable for fluorescence-guided resection with 5-ALA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 3 - <18 years
- •First radiological diagnosis of intra-axial, contrast-enhancing tumor on MRI or recurrent supratentorial intra-axial brain tumor (malignant glioma, astrocytoma, malignant ependymoma, atypical teratoid rhabdoid tumors (AT/RT), Oligodendroglioma, etc.)
- •Resection is part of therapeutic strategy with an emphasis on neurological safety
- •Informed consent by the parents or guardians and if possible assent of the patient after education of purpose and risks of study. Patients that are able to understand should provide assent to participate in the trial
- •Female adolescents: not pregnant (pregnancy test required for adolescents of child-bearing age) and not breast-feeding (for at least 24 hours after Gliolan intake). Female patients of childbearing potential and male patients who are sexually active must be practising a highly effective method of birth control up to 6 weeks after the tumor operation consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials.
排除标准
- •Extra-axial tumors such as craniopharyngioma
- •Entities precluding surgical resection
- •Acute or chronic porphyria
- •Hypersensitivity to 5-ALA or porphyrins
- •Renal insufficiency: serum creatinine > 2x upper limit of normal (ULN)
- •Hepatic insufficiency: serum bilirubin > 2x ULN, serum γ-glutamyl transferase > 2,5 x ULN, alanine transaminase (ALT) and aspartate transaminase (AST)> 2,5 ULN
- •Blood clotting: INR (international normalized ratio) out of acceptable limits
- •Other malignant disease
- •Patients with pre-existing cardiovascular diseases
- •Co-administration with other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
- •Planned administration of potentially hepatotoxic substances within 24 hours after 5-ALA administration
研究组 & 干预措施
5-Aminolevulinic Acid (5-ALA)
Application of 5-ALA oral solution followed by fluorescence-guided brain tumor resection
干预措施: 5-Aminolevulinic Acid Hydrochloride, Oral (Drug)
结局指标
主要结局
Safety of 5-ALA for fluorescence-guided resections in children and adolescents determined as incidence of adverse events of CTCAE grade III-V.
时间窗: up to 6 weeks after tumor resection
Incidence of adverse events of CTCAE grade III, IV or V (excluding chemotherapy-associated toxicities) during and after 5-ALA fluorescence-guided resections in children and adolescents
次要结局
- True positive rate of fluorescence for indicating tumor(Day 0: during the surgery)
- Correlation of residual contrast-enhancing tumor with residual fluorescence after surgery(Day 0: during the surgery)
- Determination of protoporphyrin IX (PPIX) in serum to determine interpolated maximum plasma concentration (Cmax) of PPIX.(3-6 hours, 6-9 hours and 9-12 hours after surgery)
- Determination of the percentage of patients with gros total resection and subtotal resection(up to 72h after surgery)
- Determination of protoporphyrin IX (PPIX) in serum to analyse AUC (Area under the curve) of PPIX(3-6 hours, 6-9 hours and 9-12 hours after surgery)