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

NCT ID: NCT04738162

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-25
• Study Completion Date: 2025-11-24

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.

Detailed Description

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.

Conditions

Brain Tumor, Pediatric

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

5-Aminolevulinic Acid (5-ALA)

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

Group Type: EXPERIMENTAL

5-Aminolevulinic Acid Hydrochloride, Oral

Intervention Type: 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

Interventions

5-Aminolevulinic Acid Hydrochloride, Oral

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

Intervention Type: DRUG

Other Intervention Names

Gliolan

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

photonamic GmbH & Co. KG

INDUSTRY

Sponsor Role: collaborator

medac GmbH

INDUSTRY

Sponsor Role: collaborator

Universität Münster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter Stummer, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Muenster

Locations

Universitätsklinikum Augsburg, Klinik für Neurochirurgie

Augsburg, , Germany

Universitätsklinikum Essen, Klinik für Neurochirurgie

Essen, , Germany

Universitätsmedizin Mainz, Klinik und Poliklinik für Neurochirurgie

Mainz, , Germany

Neurochirurgische Klinik der Universität München (LMU)

München, , Germany

University Hospital Münster, Klinik für Neurochirurgie

Münster, , Germany

Universitätsklinikum Tübingen, Klinik für Neurochirurgie

Tübingen, , Germany

Prinses Máxima Centrum voor kinderoncologie BV

Utrecht, , Netherlands

Countries

Germany; Netherlands

Other Identifiers

2014-005669-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UKM2013_0034

Identifier Type: -

Identifier Source: org_study_id