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

NCT04738162 | Completed Phase 2 DMC

• 2 other identifiers: UKM2013_00342014-005669-54
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Brain Tumor, Pediatric

Keywords

5-ALA; intra-axial; Fluorescence-guided resection; pediatric

Outcome Measures

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.

  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

  up to 6 weeks after tumor resection

Secondary Outcomes (5)

• True positive rate of fluorescence for indicating tumor

  Day 0: during the surgery

• Determination of the percentage of patients with gros total resection and subtotal resection

  up to 72h after 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 analyse AUC (Area under the curve) of PPIX

  3-6 hours, 6-9 hours and 9-12 hours after 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

Study Arms (1)

5-Aminolevulinic Acid (5-ALA)

EXPERIMENTAL

Application of 5-ALA oral solution followed by fluorescence-guided brain tumor resection

Drug: 5-Aminolevulinic Acid Hydrochloride, Oral

Interventions

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

Also known as: Gliolan

5-Aminolevulinic Acid (5-ALA)

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universität Münster: lead
• photonamic GmbH & Co. KG: collaborator
• medac GmbH: collaborator

Study Sites (7)

Universitätsklinikum Augsburg, Klinik für Neurochirurgie

Augsburg, 86146, Germany

Location

Universitätsklinikum Essen, Klinik für Neurochirurgie

Essen, 45147, Germany

Location

Universitätsmedizin Mainz, Klinik und Poliklinik für Neurochirurgie

Mainz, 55131, Germany

Location

Neurochirurgische Klinik der Universität München (LMU)

München, 81377, Germany

Location

University Hospital Münster, Klinik für Neurochirurgie

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen, Klinik für Neurochirurgie

Tübingen, 72076, Germany

Location

Prinses Máxima Centrum voor kinderoncologie BV

Utrecht, 3584, Netherlands

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Walter Stummer, Prof.

  University Hospital Muenster

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: February 4, 2021
• Study Start: September 25, 2020
• Primary Completion: November 24, 2025
• Study Completion: November 24, 2025
• Last Updated: December 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DE (6)