Brain Tumor, PediatricPhase 2NCT04738162
Clinical Safety Study on 5-Aminolevulinic Acid (5-ALA) in Children and Adolescents With Brain Tumors
A Phase 2 study testing 5-Aminolevulinic Acid Hydrochloride, Oral in people with Brain Tumor, Pediatric, run by Universität Münster at 7 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Brain Tumor, Pediatric
- What is being tested?
- 5-Aminolevulinic Acid Hydrochloride, Oral
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 25 Sep 2020to 24 Nov 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Germany6 sites
Universitätsklinikum Augsburg, Klinik für Neurochirurgie
Augsburg, 86146
Universitätsklinikum Essen, Klinik für Neurochirurgie
Essen, 45147
Universitätsmedizin Mainz, Klinik und Poliklinik für Neurochirurgie
Mainz, 55131
Neurochirurgische Klinik der Universität München (LMU)
München, 81377
University Hospital Münster, Klinik für Neurochirurgie
Münster, 48149
Universitätsklinikum Tübingen, Klinik für Neurochirurgie
Tübingen, 72076
Netherlands1 site
Prinses Máxima Centrum voor kinderoncologie BV
Utrecht, 3584
About this study
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.
Read the 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
- Being tested
- 5-Aminolevulinic Acid Hydrochloride, Oral
- Keywords
- 5-ALA, intra-axial, Fluorescence-guided resection, pediatric
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-Aminolevulinic Acid Hydrochloride, OralDrug
Also called Gliolan
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
| Study group | Role | What they receive |
|---|---|---|
| 5-Aminolevulinic Acid (5-ALA) | Experimental | Application of 5-ALA oral solution followed by fluorescence-guided brain tumor resection Receives: Drug: 5-Aminolevulinic Acid Hydrochloride, Oral |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 6 weeks after tumor resection
Secondary outcomes (5)
True positive rate of fluorescence for indicating tumor
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.
Measured: Day 0: during the surgery
Determination of the percentage of patients with gros total resection and subtotal resection
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.
Measured: up to 72h after surgery
Correlation of residual contrast-enhancing tumor with residual fluorescence after 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.
Measured: Day 0: during the surgery
Determination of protoporphyrin IX (PPIX) in serum to analyse AUC (Area under the curve) of PPIX
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.
Measured: 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.
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.
Measured: 3-6 hours, 6-9 hours and 9-12 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start25 Sep 2020
- Primary completion24 Nov 2025
- Study completion24 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Tumor, PediatricStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universität Münster
- Sponsor type
- University, hospital or other
- Collaborators
- photonamic GmbH & Co. KG, medac GmbH
- Responsible party
- Sponsor
- Investigators
- Walter Stummer, Prof., Principal investigator, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04738162
- Sponsor's protocol ID
- UKM2013_0034
- Other IDs
- 2014-005669-54, 2014
- Status last verified
- Nov 2025
- First submitted
- 13 May 2020
- Last updated
- 10 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Safety Study on 5-Aminolevulinic Acid (5-ALA) in Children and Adolescents With Brain Tumors
- ClinicalTrials.gov ID
- NCT04738162
- Acronym / sponsor ID
- UKM2013_0034
- Conditions
- Brain Tumor, Pediatric
- Keywords
- 5-ALA, intra-axial, Fluorescence-guided resection, pediatric
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Universität MünsterUniversity, hospital or other
- Collaborators
- photonamic GmbH & Co. KG, medac GmbH
- Study start
- 25 Sep 2020 (actual)
- Primary completion
- 24 Nov 2025 (actual)
- Study completion
- 24 Nov 2025 (actual)
- First posted
- 4 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-Aminolevulinic Acid (5-ALA) | Experimental | Drug: 5-Aminolevulinic Acid Hydrochloride, OralApplication of 5-ALA oral solution followed by fluorescence-guided brain tumor resection |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-Aminolevulinic Acid Hydrochloride, OralAlso: GliolanApplication 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 | Drug | 5-Aminolevulinic Acid (5-ALA) |
Primary outcome
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
5 secondary outcomes
True positive rate of fluorescence for indicating tumor
Time frame: Day 0: during the surgery
Determination of the percentage of patients with gros total resection and subtotal resection
Time frame: up to 72h after surgery
Correlation of residual contrast-enhancing tumor with residual fluorescence after surgery
Time frame: Day 0: during the surgery
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter Stummer, Prof. principal investigator
University Hospital Muenster
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-Aminolevulinic Acid Hydrochloride, Oral in people with Brain Tumor, Pediatric, run by Universität Münster at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2025.