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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005669-54 | EudraCT Number |
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| Name | Class |
|---|---|
| photonamic GmbH & Co. KG | INDUSTRY |
| medac GmbH | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5-Aminolevulinic Acid (5-ALA) | Experimental | Application of 5-ALA oral solution followed by fluorescence-guided brain tumor resection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-Aminolevulinic Acid Hydrochloride, Oral | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | up to 6 weeks after tumor resection |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Walter Stummer, Prof. | University Hospital Muenster | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum Augsburg, Klinik für Neurochirurgie | Augsburg | 86146 | Germany | |||
| Universitätsklinikum Essen, Klinik für Neurochirurgie |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000622 | Aminolevulinic Acid |
| ID | Term |
|---|---|
| D007982 | Levulinic Acids |
| D007651 | Keto Acids |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| 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. | 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. | 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. | 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. | 3-6 hours, 6-9 hours and 9-12 hours after surgery |
| Essen |
| 45147 |
| Germany |
| Universitätsmedizin Mainz, Klinik und Poliklinik für Neurochirurgie | Mainz | 55131 | Germany |
| Neurochirurgische Klinik der Universität München (LMU) | München | 81377 | Germany |
| University Hospital Münster, Klinik für Neurochirurgie | Münster | 48149 | Germany |
| Universitätsklinikum Tübingen, Klinik für Neurochirurgie | Tübingen | 72076 | Germany |
| Prinses Máxima Centrum voor kinderoncologie BV | Utrecht | 3584 | Netherlands |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |