Clinical trial NCT04738162: Clinical Safety Study on 5-Aminolevulinic Acid (5-ALA) in Children and Adolescents With Brain Tumors
Official title: Clinical Safety Study on 5-Aminolevulinic Acid (5-ALA) in Children and Adolescents With Brain Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Brain Tumor, Pediatric
Keywords: 5-ALA
intra-axial
Fluorescence-guided resection
pediatric
Lead sponsor: Universität Münster
Sponsor class: OTHER
Collaborators: name: photonamic GmbH & Co. KG
name: medac GmbH
First posted: 2021-02-04
Enrollment: 80
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Safety of 5-ALA for fluorescence-guided resections in children and adolescents determined as incidence of adverse events of CTCAE grade III-V.
timeFrame: up to 6 weeks after tumor resection
Secondary outcomes:
measure: True positive rate of fluorescence for indicating tumor
timeFrame: Day 0: during the surgery
measure: Determination of the percentage of patients with gros total resection and subtotal resection
timeFrame: up to 72h after surgery
measure: Correlation of residual contrast-enhancing tumor with residual fluorescence after surgery
timeFrame: Day 0: during the surgery
measure: Determination of protoporphyrin IX (PPIX) in serum to analyse AUC (Area under the curve) of PPIX
timeFrame: 3-6 hours, 6-9 hours and 9-12 hours after surgery
measure: Determination of protoporphyrin IX (PPIX) in serum to determine interpolated maximum plasma concentration (Cmax) of PPIX.
timeFrame: 3-6 hours, 6-9 hours and 9-12 hours after surgery
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg, Klinik für Neurochirurgie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Neurochirurgie
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz, Klinik und Poliklinik für Neurochirurgie
city: München
country: Germany
facility: Neurochirurgische Klinik der Universität München (LMU)
city: Münster
country: Germany
facility: University Hospital Münster, Klinik für Neurochirurgie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Klinik für Neurochirurgie
city: Utrecht
country: Netherlands
facility: Prinses Máxima Centrum voor kinderoncologie BV
Study officials:
affiliation: University Hospital Muenster
name: Walter Stummer, Prof.
role: PRINCIPAL_INVESTIGATOR
References: