This study has been transitioned to CTIS with ID 2024-517575-20-00 check the CTIS register for the current data. This study proposes a safety study in children in which tumors are operated on using fluorescence-guided resection which are similar to…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Toxicological and clinical safety by measuring the 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 with unifocal, contrast-enhancing intra-axial brain tumors, (first
diagnosis with unknown histology, recurrent with malignant neuroepithelial
histology).
Secondary outcome
1. True positive rate of fluorescence for indicating tumor.
2. Extent of resection as assessed on early post-operative MRI
3. Pharmacokinetics (determination of protoporphyrin IX 3 times within 12h
after 5-ALA administration)
Background summary
5-ALA, a biochemical precursor of heme, is specifically converted into
fluorescent porphyrins within malignant glioma cells via a series of enzymatic
reactions. These porphyrins exhibit strong fluorescence. Since malignant brain
tumors often grow by infiltrating surrounding brain, it is often difficult to
distinguish them from healthy brain tissue. By virtue of the fluorescence,
which can be visualized with a specific filter integrated into the microscope,
pathological tumor tissue and in particular residual tumor tissue become more
easily visible and, depending on the assessment of the surgeon regarding
resectability, can be removed. Thus, 5-ALA serves the purpose of an
intra-operative visualization aid. In contradistinction to other methods for
intra-operative identification of tumor tissue, identification is performed in
real-time, i.e. interruptions of the course of surgery are not necessary.
European and later, US approval, was preceded by a number of studies in adults,
which could show amongst others, that 5-ALA could be safely used with minimal
side effects, accumulated specifically in malignant glioma cells and provided
sufficient fluorescence in doses of 20 mg/kg. This intraoperative imaging tool,
which is now widely regarded as beneficial for brain tumor surgery in adults,
is often perceived as possibly beneficial in children and adolescents with
brain tumors as well.
Study objective
This study has been transitioned to CTIS with ID 2024-517575-20-00 check the CTIS register for the current data.
This study proposes a safety study in children in which tumors are operated on
using fluorescence-guided resection which are similar to those tumors usually
operated on in adults.
Based on previous findings regarding safety and the positive experience with
adults using fluorescence-guided resections with 5-ALA, the aim with this
present study protocol is to provide a more solid data basis for extending this
method to children and adolescents with brain tumors, so that they can benefit
also.
Study design
The 5-ALA study protocol is a prospective, open, single-armed, multicenter,
phase II study
Intervention
Single administration of 5-ALA prior to planned resection
Study burden and risks
It is not yet certain that 5-ALA has the same desired effect in children as in
adults. That is one of the questions of this study. Since it has yet to be
shown that 5-ALA also specifically stains tumor tissue in children, only tumor
tissue that would also be removed under white light will be removed during the
study. The administration of 5-ALA is therefore considered complementary. On
the other hand, the fluorescent tissue will make the surgeon aware of
potentially leftover resectable tissue that might otherwise have gone
unnoticed. This tissue can then be carefully examined with white light, after
which a choice can still be made on the basis of white light to remove this
tissue.
Treatment under this study may lead to previously unknown side effects/risks.
Albert Schweitzer-Campus 1, Gebäude D3
Münster 48149
DE
Albert Schweitzer-Campus 1, Gebäude D3
Münster 48149
DE
Listed location countries
Age
Inclusion criteria
- Age 3 - <18 years.
- First radiological diagnosis of intra-axial, contrast-enhancing tumor on MRI
or recurrent intra-axial brain tumor (malignant glioma, astrocytoma, malignant
ependymoma, astroblastoma, 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 craniopharyngeoma.
- 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 bilirubine > 2x ULN, serum γ-GT > 2,5 x ULN,
alanine transaminase (ALT) and aspartate transaminase (AST)> 2,5 ULN.
- Blood clotting: INR 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-517575-20-00 |
| EudraCT | EUCTR2014-005669-54-NL |
| ClinicalTrials.gov | NCT04738162 |
| CCMO | NL77803.000.22 |