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 : August 8, 2018
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 effects of two further drugs, which have been applied to millions of children and adolescents in other indications, will be compared to each other. The aim of the trial will be to investigate whether these drugs may increase the effects of radio- and chemotherapy, resulting in a better survival of the treated patients. One of these additional drugs will be valproic acid, traditionally used for treatment of seizure disorder. The other drug will be Chloroquin, a well-established drug for Malaria treatment. Recently, scientific studies provided evidence for anti-tumoral effects of both drugs: Valproat seems to be a so-called histondeacetylase inhibitor (HDAC inhibitor), controlling important genetic processes of tumor growth. Chloroquin is an autophagy inhibitor. It prevents the shutting-down of tumor cell metabolism, a strategy to ensure survival of the whole tumor by developing a resistance against radiation and antineoplastic agents.
Studies in cell culture, animals and first clinical trials in adults as well provided evidence for efficacy of valproic acid and chloroquine 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. As common for clinical trials, the treatment of the patients will be settled in a randomized manner to ensure impartiality of the investigators.
One aim of the HIT-HGG-2013 trial will be to compare the effects of Valproat and Chloroquin to each other. Additionally, the results will be compared with data of the HIT-HGG-2007 trial (children and adolescents with same diseases, only treated with simultaneous temozolomide radiochemotherapy).
|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 Drug: Temozolomide + Chloroquine||Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||198 participants|
|Intervention Model:||Parallel 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 :||January 1, 2022|
|Estimated Study Completion Date :||June 1, 2023|
Experimental: Temozolomide + Valproic acid
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
Experimental: Temozolomide + Chloroquine
Resochin junior® (Chloroquine), depending on patient weight and treatment scedule 1/2 to 3 tablets [25-150 mg] every day, p.o., 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 + Chloroquine
Chloroquine additionally to simultaneous radiochemotherapy with temozolomide
- Comparison of effects of valproine acid and chloroquine. [ Time Frame: 4.8 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 treated with additional CQ.
- Comparison of effects of valproine acid with respect to historical control group. [ Time Frame: 4.8 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.
- Comparison of effects of chloroquine with respect to historical control group. [ Time Frame: 4.8 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, DIPG, and gliomatosis cerebri differs for children treated with additional CQ 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 firstname.lastname@example.org|
|Contact: Michael Frühwald, Prof.|
|Evangelisches Krankenhaus Bielefeld||Recruiting|
|Contact: Norbert Jorch, Dr.|
|Contact: Carola Weber, Dr.|
|Klinikum Bremen-Mitte gGmbH||Recruiting|
|Contact: Arnulf Pekrun, Prof.|
|Klinikum Chemnitz gGmbH||Recruiting|
|Contact: André Hofmann, Dr.|
|Carl-Thiem-Klinikum Cottbus gGmbH||Recruiting|
|Contact: Georg Schwabe, PD Dr.|
|Sana Kliniken Duisburg GmbH - Wedau Kliniken||Recruiting|
|Contact: Tanja Höll, Dr.|
|Contact: Markus Metzler, Prof.|
|Contact: Charlotte Niemeyer, Prof.|
|Contact: Holger Lode, Prof.|
|Contact: Christof Kramm, Prof.|
|Contact: Toralf Bernig, Dr.|
|Universitätsklinikum des Saarlandes||Recruiting|
|Contact: Norbert Graf, Prof.|
|Gesundheit Nordhessen - Klinikum Kassel||Recruiting|
|Contact: Michaela Nathrath, Prof.|
|Contact: Holger Christiansen, Prof.|
|UMM Universitätsmedizin Mannheim||Recruiting|
|Contact: Matthias Dürken, PD Dr.|
|Johannes Wesling Klinikum Minden||Recruiting|
|Contact: Bernhard Erdlenbruch, Prof.|
|Contact: Ronald Sträter, PD Dr.|
|Klinikum Oldenburg gGmbH||Recruiting|
|Contact: Hermann Müller, Prof.|
|Contact: Marcus Jakob, Dr.|
|ASKLEPIOS Klinik St. Augustin||Recruiting|
|Sankt Augustin, Germany|
|Contact: Harald Reinhard, PD Dr.|
|Klinikum Stuttgart - Olgahospital||Recruiting|
|Contact: Stefan Bielack, Prof.|
|Contact: Martin Ebinger, PD Dr.|
|Study Chair:||Christof Kramm, Prof., MD||University of Göttingen|