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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04738162

Studienbeginn:
September 2020

Letztes Update:
04.02.2021

Wirkstoff:
5-Aminolevulinic Acid Hydrochloride, Oral

Indikation (Clinical Trials):
Brain Neoplasms

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
Phase 2

Sponsor:
Westfälische Wilhelms-Universität Münster

Collaborator:
photonamic GmbH & Co. KG, medac GmbH,

Studienleiter

Walter Stummer, Prof.
Principal Investigator
University Hospital Muenster

Kontakt

Michael Schwake, Dr.
Kontakt:
Phone: +49 251 83
Phone (ext.): 47484 /47472
E-Mail: Michael.Schwake@ukmuenster.de
» Kontaktdaten anzeigen
Walter Stummer, Prof. Dr.
Kontakt:
Phone: +49 251 83
Phone (ext.): 47472
E-Mail: Walter.Stummer@ukmuenster.de
» Kontaktdaten anzeigen

Studienlocations
(3 von 4)

Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Age 3 - <18 years

- First radiological diagnosis of intra-axial, supratentorial 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:

- Posterior fossa tumors

- Extra-axial tumors such as craniopharyngioma

- Germ cell tumor or 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

Studien-Rationale

Primary outcome:

1. 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



Secondary outcome:

1. True positive rate of fluorescence for indicating tumor (Time Frame - Day 0: during the surgery):
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.

2. Determination of the percentage of patients with gros total resection and subtotal resection (Time Frame - up to 72h after surgery):
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.

3. Correlation of residual contrast-enhancing tumor with residual fluorescence after surgery (Time Frame - Day 0: during the 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.

4. 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):
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.

5. 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):
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.

Geprüfte Regime

  • 5-Aminolevulinic Acid Hydrochloride, Oral (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

Quelle: ClinicalTrials.gov


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