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About
The HIT-HGG-2013 trial offers an innovative high-quality diagnostics and science program for children and adolescents >3 years, suffering from one of the following types of high grade gliomas:
In addition to standard treatment (radiotherapy and temozolomide chemotherapy) the effect of valproic acid which is traditionally used for treatment of seizure disorder, will be investigated. The aim of the trial will be to investigate whether this drug may increase the effects of radio- and chemotherapy, resulting in a better survival of the treated patients. Scientific studies provided evidence for anti-tumoral effects of valproic acid: the drug seems to be a so-called histondeacetylase inhibitor (HDAC inhibitor), controlling important genetic processes of tumor growth.
Studies in cell culture, animals and first clinical trials in adults as well provided evidence for efficacy of valproic acid in the treatment of glioblastoma. Due to this we hope children and adolescents suffering from GBM, DMG, AA, DIPG und GC will benefit from the treatment, too.
The aim of the HIT-HGG-2013 trial will be to compare the effects of Valproic acid with data of the HIT-HGG-2007 trial (children and adolescents with same diseases, only treated with simultaneous temozolomide radiochemotherapy).
In the present study, it was originally planned to investigate the therapeutic efficiency and safety of valproic acid and the autophagy inhibitor chloroquine, both in addition to temozolomide therapy. Since distribution of Resochin junior (chloroquine phosphate) was terminated, recruitment of new patients was stopped on August 8, 2019. For continuation of the trial, the chloroquine arm was closed but the patients already recruited in this arm will be followed up.
Full description
Indication:
First-line treatment of high grade gliomas, diffuse intrinsic pontine glioma, and gliomatosis cerebri in paediatric patients < 18 years of age.
Background:
Based on published preclinical and clinical results regarding the potential therapeutic benefit of adult and pediatric high grade glioma patients receiving the histone deacetylase (HDAC) inhibitor valproic acid (VPA; Barker et al. 2013; Wolff et al. 2008, 2011; Felix et al. 2011; Su et al. 2011; Rokes et al. 2010; Masoudi et al. 2008; Guthrie et al. 2013; Weller et al. 2011) in addition to radiochemotherapy, the present trial is aimed to investigate if the addition of VPA to radiochemo- and maintenance therapy with temozolomide (Stupp et al. 2005; Cohen et al. 2011a, b) provides a survival advantage in comparison to radiochemo- and maintenance therapy with temozolomide alone. Therapeutic efficiency of VPA will be evaluated by comparison with a historical patient control from the previous trial HIT-HGG-2007 with temozolomide radiochemo- and maintenance therapy alone. Besides therapeutic efficiencies as indicated by event-free survival (EFS) and overall survival (OS) treatment-related toxicities will also be analysed.
Therapy:
TMZ and VPA will be studied as investigational medicinal products in the present trial.
After start of VPA induction with simultaneous radiochemotherapy:
Primary end point : Event-free survival
Biometry (regarding the primary objectives):
Confirmatory statistical design:
Statistical tests: adaptive Log-rank test / (conventional) Log-rank test
Multiple Significance level α(overall) = 5% Power = 80% Assumed 6 months EFS-rates = 55% vs. 70%
Multiple Testing: No Multiplicity Problem in this trial.
Estimated sample sizes:
About 167 recruitments at final analysis
Patient recruitment will be performed for 5,4 years. Individual follow-up (including study treatment) is required for this protocol for at least 1 year and 30 days after study entry. Long-term follow-up is strongly recommended and will be organised according to national guidelines and recommendations.
Financial support:
Deutsche Kinderkrebsstiftung, Bonn, Germany
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167 participants in 1 patient group
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Central trial contact
Christof Kramm, Prof., MD
Data sourced from clinicaltrials.gov
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