International Cooperative Phase III Trial of the HIT-HGG Study Group (HIT-HGG-2013)

NCT03243461 | Unknown Phase 3 DMC

• 2 other identifiers: 011532013-004187-56
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 51

Brief Summary

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

Conditions

Glioblastoma WHO Grade IV; Diffuse Midline Glioma Histone 3 K27M WHO Grade IV; Anaplastic Astrocytoma WHO Grade III; Diffuse Intrinsic Pontine Glioma; Gliomatosis Cerebri

Keywords

Glioblastoma; high grade glioma; brain tumor; Anaplastic astrocytoma; DIPG; Gliomatosis cerebri; Diffuse midline glioma; Valproic acid; Temozolomide

Outcome Measures

Primary Outcomes (1)

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

  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.

  5.4 years

Study Arms (1)

Temozolomide + Valproic acid

EXPERIMENTAL

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

Interventions

Temozolomide + Valproic Acid DRUG

Valproic acid additionally to simultaneous radiochemotherapy with temozolomide

Temozolomide + Valproic acid

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newly diagnosed, previously untreated diffuse paediatric high grade glioma with central neuropathological review including paedHGG (WHO grade IV) and anaplastic astrocytoma (WHO grade III).
• 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

You may not qualify if:

• Pre-treatment of paedHGG (WHO grade IV), anaplastic astrocytoma (WHO grade III), 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 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), e.g. Alpers-Huttenlocher syndrome, as well as suspected POLGrelated disorders in children under the age of two years

Sponsors & Collaborators

• University of Göttingen: lead
• Deutsche Kinderkrebsstiftung: collaborator
• Hannover Medical School: collaborator

Study Sites (51)

Universitätsklinik RWTH Aachen

Aachen, Germany

RECRUITING

Klinikum Augsburg

Augsburg, Germany

RECRUITING

Charité Universitätsmedizin Berlin

Berlin, Germany

RECRUITING

HELIOS Klinikum Berlin Buch

Berlin, Germany

RECRUITING

Evangelisches Krankenhaus Bielefeld

Bielefeld, Germany

RECRUITING

Universitätsklinikum Bonn

Bonn, Germany

RECRUITING

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, Germany

RECRUITING

Klinikum Bremen-Mitte gGmbH

Bremen, Germany

RECRUITING

Kliniken der Stadt Köln gGmbH

Cologne, Germany

RECRUITING

Carl-Thiem-Klinikum Cottbus gGmbH

Cottbus, Germany

RECRUITING

Klinikum Dortmund gGmbH

Dortmund, Germany

RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany

RECRUITING

Sana Kliniken Duisburg GmbH - Wedau Kliniken

Duisburg, Germany

RECRUITING

HELIOS Klinikum Erfurt GmbH

Erfurt, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, Germany

RECRUITING

Universitätsklinikum Essen

Essen, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

RECRUITING

Universitätsklinikum Gießen und Marburg GmbH

Giessen, Germany

RECRUITING

Universitätsmedizin Göttingen

Göttingen, Germany

RECRUITING

Universitätsmedizin Greifswald

Greifswald, Germany

RECRUITING

Universitätsklinikum Halle

Halle, Germany

RECRUITING

Universitätsklinikum Hamburg

Hamburg, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Germany

RECRUITING

Angelika-Lautenschläger-Klinik

Heidelberg, Germany

RECRUITING

SLK-Kliniken Heilbronn GmbH

Heilbronn, Germany

RECRUITING

Gemeinschaftskrankenhaus Herdecke

Herdecke, Germany

RECRUITING

Universitätsklinikum des Saarlandes

Homburg, Germany

RECRUITING

Universitätsklinikum Jena

Jena, Germany

RECRUITING

Städtisches Klinikum Karlsruhe

Karlsruhe, Germany

RECRUITING

Gesundheit Nordhessen - Klinikum Kassel

Kassel, Germany

RECRUITING

UKSH Kiel

Kiel, Germany

RECRUITING

Gemeinschaftsklinikum Mittelrhein gGmbH

Koblenz, Germany

RECRUITING

HELIOS Klinikum Krefeld

Krefeld, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, Germany

RECRUITING

UKSH Campus Lübeck

Lübeck, Germany

RECRUITING

Universitätsklinikum Magdeburg A. ö. R.

Magdeburg, Germany

RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Germany

RECRUITING

UMM Universitätsmedizin Mannheim

Mannheim, Germany

RECRUITING

Johannes Wesling Klinikum Minden

Minden, Germany

RECRUITING

Technische Universität München / Klinikum Schwabing

München, Germany

RECRUITING

Universitätsklinikum Münster

Münster, Germany

RECRUITING

Klinikum Oldenburg gGmbH

Oldenburg, Germany

RECRUITING

Universitätsklinikum Regensburg

Regensburg, Germany

RECRUITING

Universitäts-Kinder- und Jugendklinik Rostock

Rostock, Germany

ACTIVE NOT RECRUITING

ASKLEPIOS Klinik St. Augustin

Sankt Augustin, Germany

RECRUITING

HELIOS Kliniken Schwerin GmbH

Schwerin, Germany

RECRUITING

Klinikum Stuttgart - Olgahospital

Stuttgart, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, Germany

RECRUITING

Universitätsklinik Würzburg

Würzburg, Germany

RECRUITING

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Neoplasms, Neuroepithelial; Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma

Interventions

Temozolomide; Valproic Acid

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Christof Kramm, Prof., MD

  University of Göttingen

  STUDY CHAIR

Central Study Contacts

Christof Kramm, Prof., MD

CONTACT

49(0)551 39 63081; christof.kramm@med.uni-goettingen.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating investigator

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 9, 2017
• Study Start: July 17, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (51)