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Report for Clinical Trial NCT03243461

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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)

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: 1. glioblastoma WHO grade IV (GBM) 2. diffuse midlineglioma histone 3 K27M mutated WHO grade IV (DMG) 3. anaplastic astrocytoma WHO grade III (AA) 4. diffuse intrinsic pontine glioma (DIPG) 5. 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).

NCT03243461 Glioblastoma WHO Grade IV Diffuse Midline Glioma Histone 3 K27M WHO Grade IV Anaplastic Astrocytoma WHO Grade III Diffuse Intrinsic Pontine Glioma Gliomatosis Cerebri
MeSH:Glioblastoma Glioma Astrocytoma Neoplasms, Neuroepithelial
HPO:Astrocytoma Glioblastoma multiforme Glioma Neuroepithelial neoplasm Subependymal giant-cell astrocytoma

2 Interventions

Name: Temozolomide + Valproic Acid

Description: Valproic acid additionally to simultaneous radiochemotherapy with temozolomide
Type: Drug
Group Labels: 1

Temozolomide + Valproic acid

Name: Temozolomide + Chloroquine

Description: Chloroquine additionally to simultaneous radiochemotherapy with temozolomide
Type: Drug
Group Labels: 1

Temozolomide + Chloroquine


Primary Outcomes

Description: 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.

Measure: Comparison of effects of valproine acid and chloroquine.

Time: 4.8 years

Description: 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.

Measure: Comparison of effects of valproine acid with respect to historical control group.

Time: 4.8 years

Description: 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.

Measure: Comparison of effects of chloroquine with respect to historical control group.

Time: 4.8 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 K27M

International Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013) 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: 1. glioblastoma WHO grade IV (GBM) 2. diffuse midlineglioma histone 3 K27M mutated WHO grade IV (DMG) 3. anaplastic astrocytoma WHO grade III (AA) 4. diffuse intrinsic pontine glioma (DIPG) 5. gliomatosis cerebri (GC) For 1.-3. --- K27M ---

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 - Severe manifest hepatic disease including hepatic porphyria as well as personal or family history of severe hepatic dysfunction, especially drug-related - Severe pancreatic disease - Severe hepatic disease - Lethal hepatic dysfunction in a sibling during valproic acid treatment - Known urea cycle defect - Severe coagulation disorders (in regards to thrombopenia see prerequisite for blood cell count before starting treatment) - Retinopathy and restricted visual fields (Exception: Brain tumour-related changes of visual fields) - Glucose-6-phosphate dehydrogenase deficiency (favism) - Myasthenia gravis - Known porphyria - Valproic acid as antiepileptc drug for any pre-existing epilepsy - Chloroquine or hydroxycloroquine as pre-existing and ongoing medication for malaria, lupus erythematodes, or any other medical reason Glioblastoma WHO Grade IV Diffuse Midline Glioma Histone 3 K27M WHO Grade IV Anaplastic Astrocytoma WHO Grade III Diffuse Intrinsic Pontine Glioma Gliomatosis Cerebri Glioblastoma Glioma Astrocytoma Neoplasms, Neuroepithelial Indication: First-line treatment of high grade gliomas, diffuse intrinsic pontine glioma, and gliomatosis cerebri in paediatric patients < 18 years of age. --- K27M ---



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