International Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013) (HIT-HGG-2013)
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|ClinicalTrials.gov Identifier: NCT03243461|
Recruitment Status : Recruiting
First Posted : August 9, 2017
Last Update Posted : June 6, 2022
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:
- glioblastoma WHO grade IV (GBM)
- diffuse midlineglioma histone 3 K27M mutated WHO grade IV (DMG)
- anaplastic astrocytoma WHO grade III (AA)
- diffuse intrinsic pontine glioma (DIPG)
- gliomatosis cerebri (GC) For 1.-3. diagnosis has to be confirmed by neuropathological survey, for 4. and 5. diagnosis has to be confirmed by neuroradiological survey.
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma WHO Grade IV Diffuse Midline Glioma Histone 3 K27M WHO Grade IV Anaplastic Astrocytoma WHO Grade III Diffuse Intrinsic Pontine Glioma Gliomatosis Cerebri||Drug: Temozolomide + Valproic Acid||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||167 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.(HIT-HGG-2013)|
|Actual Study Start Date :||July 17, 2018|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Experimental: Temozolomide + Valproic acid
E.g. Valproat-neuraxpharm®, Valproat-neuraxpharm® Lösung, Ergenyl®, Ergenyl®-Lösung oder Orfiril® Saft (Valproic acid), [10 mg/kg/d] tablet oder juice, p.o., every day in parallel to simultaneous radiochemotherapy with cytostatic drug Temodal (Temozolomid): [75 mg/m2/d] during simultaneous radiochemotherapy (7 days a week, max. 49 days); [150-200 mg/m2/d] during consolidation therapy (for 5 days every 28 days, 12 cycles), tablets, p.o. (or powder for preparation of an intravenously applicable solution).
Drug: Temozolomide + Valproic Acid
Valproic acid additionally to simultaneous radiochemotherapy with temozolomide
- Comparison of effects of valproine acid with respect to historical control group. [ Time Frame: 5.4 years ]To confirm that the Event-Free Survival (EFS) in patients ≥ 3 years of age with paed HGG WHO grade IV, anaplastic astrocytoma WHO grade III (AAIII), DIPG, and gliomatosis cerebri differs for children treated with additional VPA compared to children in the historical HIT-HGG-2007 study sample.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03243461
|Contact: Christof Kramm, Prof., MD||49(0)551 39 email@example.com|
|Study Chair:||Christof Kramm, Prof., MD||University of Göttingen|