Skip to main content
OpenTrials
Completed

NCT Number: NCT04738162

Clinical Safety Study on 5-Aminolevulinic Acid (5-ALA) in Children and Adolescents With Brain Tumors

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Brain Tumor, Pediatric Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms

Age range

3 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Universitätsklinikum Augsburg, Klinik für Neurochirurgie, Augsburg, Germany

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

5-Aminolevulinic Acid Hydrochloride, Oral

Drug

Application of 5-ALA oral solution (20mg/kg bw) 4 hours (range 3.5-4.5 hours) prior to anesthesia followed by fluorescence-guided tumor resection Tumor resection is performed conventionally using a surgical microscope. A change from white light to blue light is possible at anytime to make the fluorescence visible

Other names: Gliolan

Primary outcomes

  1. Safety of 5-ALA for fluorescence-guided resections in children and adolescents determined as incidence of adverse events of CTCAE grade III-V.

    Time frame: 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

Secondary outcomes

  1. True positive rate of fluorescence for indicating tumor

    Time frame: Day 0: during the surgery

    Biopsies will be taken during tumor resection. The true positive rate of 5 ALA induced fluorescence for three different tumor regions, i.e. the number of fluorescing tumor samples containing tumor cells divided by the number of all tumor samples from 1) the tumor bulk, 2) the border area and 3) the suspected infiltration zone. A stratification will be performed depending on whether surgery is for newly diagnosed or recurrent tumor.

  2. Determination of the percentage of patients with gros total resection and subtotal resection

    Time frame: up to 72h after surgery

    For every patient in whom a complete resection of enhancing tumor is expected a priori, it will be assessed whether there is residual contrast-enhancement or not on early post-operative MRI. The volume of contrast-enhancing tumor on early post-operative MRI (up to 72h after surgery) in cm3 will be determined. If the volume is < 0.175cm3, the patient will be classified as "gros total resection". If the volume is >0.175cm3, the patient will be classified as "subtotal resection". Percentage of patients for both groups will be determined.

  3. Correlation of residual contrast-enhancing tumor with residual fluorescence after surgery

    Time frame: Day 0: during the surgery

    For both groups (patients with gros total and subtotal resection) the percentage of patients with residual fluorescence at end of surgery, as determined during the surgery by the operating surgeon (yes/no), will be calculated.

  4. Determination of protoporphyrin IX (PPIX) in serum to analyse AUC (Area under the curve) of PPIX

    Time frame: 3-6 hours, 6-9 hours and 9-12 hours after surgery

    The investigators aim to determine 5-ALA pharmacokinetics in children and adolescents from PPIX plasma levels in order to assess if the pharmacokinetics differ between adults and children. Pharmacokinetic data will be analyzed using population pharmacokinetic software approach using nonlinear-mixed effects modelling (NONMEM). In order to assess if the pharmacokinetics are similar, the area under the curve (AUC) for PPIX as a measure of 5-ALA exposure will be calculated. For this purpose protoporphyrin IX will be measured in serum 3 times within 12h after 5-ALA-administration.

  5. Determination of protoporphyrin IX (PPIX) in serum to determine interpolated maximum plasma concentration (Cmax) of PPIX.

    Time frame: 3-6 hours, 6-9 hours and 9-12 hours after surgery

    Protoporphyrin IX will be measured in serum 3 times within 12h after 5-ALA-administration. Pharmacokinetic data will be analyzed using population pharmacokinetic software approach using nonlinear-mixed effects modelling (NONMEM). Using the model, interpolated maximum plasma concentration (Cmax) of PPIX will be determined for every patient.

Sponsors and collaborators

Lead sponsor

Universität Münster

Other

Collaborators

  • medac GmbH
  • photonamic GmbH & Co. KG

Registry information

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Feb 4, 2021
Registry last updated
Dec 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.