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

Universität Münster

Status and phase

Completed

Phase 2

Conditions

Brain Tumor, Pediatric

Treatments

Drug: 5-Aminolevulinic Acid Hydrochloride, Oral

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04738162

UKM2013_0034

2014-005669-54 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

78 patients

Sex

All

Ages

3 to 17 years old

Volunteers

No Healthy Volunteers

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