International cooperative Phase III trial of the HIT-HGG study group for the treatment of high grade glioma, diffuse intrinsic pontine glioma, and gliomatosis cerebri in children and adolescents < 18 years.
- Conditions
- brain tumorshigh grade gliomadiffuse intrinsic pontine gliomagliomatosis cerebri10029211
- Registration Number
- NL-OMON54159
- Lead Sponsor
- Georg-August-Universität Göttingen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
•Newly diagnosed, previously untreated diffuse high grade glioma with central
neuropathological review including WHO grade IV/CNS WHO grade 4 and WHO grade
III/CNS WHO grade 3 diffuse high grade gliomas as well as diffuse high grade
gliomas without a distinct grade.
•Newly diagnosed, previously untreated diffuse intrinsic pontine glioma with
central neuroradiological review
•Newly diagnosed, previously untreated gliomatosis cerebri of all tumour grades
with central neuroradiological review
•Patient >= 3 years and < 18 years of age at time of diagnosis
•Written informed consent of the patient and/or the patient's parents or legal
guardian according to national laws
•Pre-treatment of diffuse WHO grade IV/CNS WHO grade 4 and WHO grade III/CNS
WHO grade 3 high grade gliomas, diffuse high grade gkiomas without a distinct
grade, diffuse intrinsic pontine glioma (as confirmed by neuroradiological
review), and gliomatosis cerebri (as confirmed by neuroradiological review).
•Known hypersensitivity or contraindication to study drugs and/or dacarbazine
•Prior chemotherapy within the last 30 days before HIT-HGG-2013 treatment or
radiotherapy which prevents adequate performance of radiotherapy as outlined by
the present protocol. This may mainly apply to patients with secondary high
grade glioma after previous malignant brain tumour, e.g. medulloblastoma,
ependymoma, craniopharyngeoma. If previous treatment does not prevent the
adequate performance of the outlined treatment protocol patients with secondary
high grade glioma will be eligible for the present trial.
•Other (simultaneous) malignancies
•Pregnancy and / or lactation
•Patients who are sexually active refusing to use effective contraception (oral
contraception, intrauterine devices, barrier method of contraception in
conjunction with spermicidal jelly)
•Current or recent (within 30 days prior to start of trial treatment) treatment
with another investigational drug or participation in another investigational
trial.
•Clinical (e.g. a constitutional mismatch repair deficiency score >= 3; Wimmer
et al. 2014) and/or other hints (e.g. absent intratumoral immunohistochemical
expression of at least one of the MLH1, MSH2, MSH6, or PMS2 mismatch repair
proteins and/or high microsatellite instability) for an underlying biallelic
(constitutional) mismatch repair deficiency (bMMRD/CMMRD) or a heterozygous
mismatch repair deficiency (hereditary non-polyposis colon cancer
syndrome/HNPCC syndrome/Lynch syndrome): These patients and their relatives
should be offered human genetic counseling and rapid genetic diagnostics to
confirm or rule out these conditions. These patients might not benefit from the
present study treatment but maybe from other therapeutic strategies (Bouffet et
al. 2016). Since patients with clinically suspected neurofibromatosis type 1
may display similar symptoms as in CMMRD, patients with clinically suspected
neurofibromatosis type 1 should be also checked for CMMRD as suggested above.
•Very poor clinical condition as defined by demand of mechanical ventilation
and/or demand for intravenous catecholamines and/or very severe neurological
damage equivalent to a coma and/or tetraplegia with complete incapability for
communication (deafness, blindness, mutism)
•Known severe concomitant diseases (e.g. immune deficiency syndrome; known
tumour predisposition syndromes which do not affect adequate performance of the
trial represent no exclusion criterion a priori
•Known HIV positivity
•Known severe manifest hepatic disease including hepatic porphyria as well as
personal or family history of severe hepatic dysfunction, especially
drug-related
•Known severe pancreatic disease
•Known lethal hepatic dysfunction in a sibling during valproic acid treatment
•Known urea cycle defect
•Known mitochondrial diseases caused by genetic mutations within the gene
coding for the enzyme polymerase gamma (POLG)
•Known severe coagulation disorders (in regards to thrombopenia see
prereq
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method