Clinical safety study on 5-Aminolevulinic acid (5-ALA) in children and adolescents with brain tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaet Muenster

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Aug 2020 → 24 Nov 2025

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

photonamic GmbH & Co. KG Germany · medac Gesellschaft für klinische Spezialpräparate mbH Germany

External identifiers

EU CT number

2024-517575-20-00

EudraCT number

2014-005669-54

ClinicalTrials.gov

NCT04738162

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To determine the safety of 5-ALA for fluorescence-guided resections in children and adolescents with intra-axial brain tumors

Secondary objectives 3

1. To determine the true positive rate of 5-ALA for identifying tumor, defined as the number of fluorescing biopsies containing tumor cells divided by the number of all fluorescing biopsies.
2. Degree of resection, determined as the volume of contrast-enhancing tumor on early post-operative MRI after a priori definition of whether complete resection would be aim of surgery.
3. Determine 5-ALA pharmacokinetics in children and adolescents, as assessed from PPIX plasma levels 3 times within 12h after administration of 5-ALA, provided that parents or guardians agree to blood sampling. Blood sampling is on a voluntary basis and independent of study participation.

Conditions and MedDRA coding

different types of brain tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age 3 - <18 years
2. First radiological diagnosis of intra-axial, contrast-enhancing tumor on MRI or recurrent intra-axial brain tumor (malignant glioma, astrocytoma, malignant ependymoma, AT/RT, Oligodendroglioma, etc.)
3. Resection is part of therapeutic strategy with an emphasis on neurological safety
4. 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
5. Female adolescents: not pregnant (pregnancy test required for adolescents of childbearing age) or breast-feeding (for at least 24 hours after Gliolan intake)
6. 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 (see section 7.4).

Exclusion criteria 11

1. Extraaxial tumors such as craniopharyngeoma
2. Entities precluding surgical resection
3. Acute or chronic porphyria
4. Hypersensitivity to 5-ALA or porphyrins
5. Renal insufficiency: serum creatinine > 2x upper limit of normal (ULN)
6. Hepatic insufficiency: serum bilirubine > 2x ULN, serum γ-GT > 2,5 x ULN, alanine transaminase (ALT) and aspartate transaminase (AST) > 2,5x ULN
7. Blood clotting: INR out of acceptable limits
8. Other malignant disease
9. Patients with pre-existing cardiovascular diseases
10. Co-administration with other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)
11. Planned administration of potentially hepatotoxic substances within 24 hours after 5-ALA administration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint is the incidence of adverse events of CTCAE Version 4.0 grades III, IV or V (excluding chemotherapy-associated toxicities) during and after 5-ALA fluorescence-guided resections in children and adolescents with unifocal, , contrast-enhancing intra-axial brain tumors.

Secondary endpoints 3

1. The true positive rate of 5-ALA-induced fluorescence for predicting bulk tumor tissue, or tumor at the border area or infiltrating tumor will be determined from histopathology of fluorescing tissue biopsies. Only tissue, which is destined for removal under white light conditions due to its appearance and resectability, is to be assessed. The location of residual tissue which is left unresected and which shows fluorescence will be documented by the neurosurgeon.
2. For the determination of the degree of 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 visible on early post-operative MRI. The relationship between residual fluorescence and possible residual enhancing tumor will be described qualitatively.
3. If possible and if consent is given, blood samples will be collected 3 times within 12h after administration of 5-ALA for determination of PPIX in plasma to elucidate 5-ALA metabolism in children and adolescents.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Muenster

Sponsor organisation

Universitaet Muenster

Address

Schlossplatz 2, Schlossbezirk Schlossbezirk

City

Muenster

Postcode

48149

Country

Germany

Scientific contact point

Organisation

Universitaet Muenster

Contact name

Prof. Walter Stummer

Public contact point

Organisation

Universitaet Muenster

Contact name

Prof. Walter Stummer

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications