NCT03243461: HIT-HGG-2013

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

Status unknown Phase 3 Last updated 6 June 2022

What this trial tests

Phase 3 trial testing Temozolomide + Valproic Acid in Glioblastoma WHO Grade IV in 167 participants. Status unknown.

Timeline

17 July 2018

Primary endpoint
31 December 2023

31 December 2023

Quick facts

Lead sponsor	University of Göttingen
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	167
Start date	17 July 2018
Primary completion	31 December 2023
Estimated completion	31 December 2023
Sites	51 locations across Germany

Drugs / interventions tested

• Temozolomide + Valproic Acid — full drug profile →

Conditions studied

• Glioblastoma WHO Grade IV — all drugs for Glioblastoma WHO Grade IV →
• Diffuse Midline Glioma Histone 3 K27M WHO Grade IV — all drugs for Diffuse Midline Glioma Histone 3 K27M WHO Grade IV →
• Anaplastic Astrocytoma WHO Grade III — all drugs for Anaplastic Astrocytoma WHO Grade III →
• Diffuse Intrinsic Pontine Glioma — all drugs for Diffuse Intrinsic Pontine Glioma →

Sponsor

University of Göttingen

Who can join

Adults 3 to 17, any sex, with Glioblastoma WHO Grade IV or Diffuse Midline Glioma Histone 3 K27M WHO Grade IV. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer.
   Li C, Xu X, Wei S, Jiang P, et al · · 2021 · cited 259× · PMID 33504575 · DOI 10.1136/jitc-2020-001341
2. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
   Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
3. Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents.
   Verbaanderd C, Maes H, Schaaf MB, Sukhatme VP, et al · · 2017 · cited 198× · PMID 29225688 · DOI 10.3332/ecancer.2017.781
4. Chloroquine combined with concurrent radiotherapy and temozolomide for newly diagnosed glioblastoma: a phase IB trial.
   Compter I, Eekers DBP, Hoeben A, Rouschop KMA, et al · · 2021 · cited 97× · PMID 32866424 · DOI 10.1080/15548627.2020.1816343
5. Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.
   Zeng Z, Fu M, Hu Y, Wei Y, et al · · 2023 · cited 93× · PMID 37853437 · DOI 10.1186/s12943-023-01877-w
6. Chloroquine against malaria, cancers and viral diseases.
   Zhou W, Wang H, Yang Y, Chen ZS, et al · · 2020 · cited 85× · PMID 32947043 · DOI 10.1016/j.drudis.2020.09.010
7. Role of Radiation Therapy in the Management of Diffuse Intrinsic Pontine Glioma: A Systematic Review.
   Gallitto M, Lazarev S, Wasserman I, Stafford JM, et al · · 2019 · cited 73× · PMID 31360809 · DOI 10.1016/j.adro.2019.03.009
8. New drugs are not enough‑drug repositioning in oncology: An update.
   Armando RG, Mengual Gómez DL, Gomez DE. · · 2020 · cited 72× · PMID 32124955 · DOI 10.3892/ijo.2020.4966