NCT03666559: AGIR

Treatment With Azacitidine of Recurrent Gliomas With IDH1/2 Mutation

Status unknown Phase 2 Last updated 29 February 2024

What this trial tests

Phase 2 trial testing Azacitidine in Recurrent IDH1/2 Mutated Glioma in 8 participants. Status unknown.

Timeline

22 September 2020

Primary endpoint
23 February 2023

23 March 2024

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	22 September 2020
Primary completion	23 February 2023
Estimated completion	23 March 2024
Sites	1 location across France

Drugs / interventions tested

• Azacitidine (azacitidine) — full drug profile →

Conditions studied

• Recurrent IDH1/2 Mutated Glioma — all drugs for Recurrent IDH1/2 Mutated Glioma →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Recurrent IDH1/2 Mutated Glioma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Glioma are the most commun frequent brain tumour. Mutation of Isocitrate DeHydrogenase IDH1 or IDH2 genes affect 40% of gliomas, mostly grade II and III gliomas. Despite IDH mutated gliomas (IDHm glioma) have a better prognosis compared to the IDH wild type counterparts, they invariably recur after standard treatment with radiotherapy and alkylating agent. IDH mutation results in the accumulation of D-2 hydroxyglutarate (D2HG) produced by the IDH mutant enzyme. D2HG acts as a competitive inhibitor of the alphaketoglutarate cofactor in a wide range of cellular reactions, including Ten-eleven translocation (TET) family enzymes and histone demethylases, resulting in DNA hypermethylation (CIMP phenotype) and histone hypermethylation. Preclinical data have shown a dramatic anti-tumor effect of hypomethylating drugs as 5-azacytidine on IDH1 mutated human gliomas. These hypomethylating drugs are routinely used in myelodysplasic syndrome (MDS) and are well tolerated.

The AGIR Trial will be a phase II, non-comparative, open label, non randomised monocentric trial evaluating efficacy of a treatment by azacitidine in recurrent IDHm gliomas. The main objective is to evaluate the efficacy of azacitidine according to the RANO criteria on progression-free survival at 6 months, evaluated according to the RANO criteria. Given the slow mode of action of treatment, it is proposed to include only patients whose life expectancy at inclusion is greater than 9 months.

A 6-month progression-free survival of less than 15% will be inefficient. The minimum efficiency must be at least 30%. An interim analysis (according to Fleming's method) will be performed when 19 patients have been included and followed up to 6 months. If the interim analysis is inconclusive, 36 additional patients will be included. The maximum number of analysable patients to include is 55.

Publications & conference data

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

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics.
   Golub D, Iyengar N, Dogra S, Wong T, et al · · 2019 · cited 176× · PMID 31165048 · DOI 10.3389/fonc.2019.00417
3. Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions.
   Miller JJ, Gonzalez Castro LN, McBrayer S, Weller M, et al · · 2023 · cited 158× · PMID 36239925 · DOI 10.1093/neuonc/noac207
4. Isocitrate Dehydrogenase Mutations in Glioma: From Basic Discovery to Therapeutics Development.
   Huang J, Yu J, Tu L, Huang N, et al · · 2019 · cited 86× · PMID 31263678 · DOI 10.3389/fonc.2019.00506
5. <i>IDH</i> Mutations in Glioma: Double-Edged Sword in Clinical Applications?
   Kayabolen A, Yilmaz E, Bagci-Onder T. · · 2021 · cited 58× · PMID 34356864 · DOI 10.3390/biomedicines9070799
6. Isocitrate Dehydrogenase Mutations in Glioma: Genetics, Biochemistry, and Clinical Indications.
   Liu Y, Lang F, Chou FJ, Zaghloul KA, et al · · 2020 · cited 50× · PMID 32825279 · DOI 10.3390/biomedicines8090294
7. Targeting IDH-Mutant Glioma.
   Miller JJ. · · 2022 · cited 45× · PMID 35476295 · DOI 10.1007/s13311-022-01238-3
8. Therapeutic Targets in Glioblastoma: Molecular Pathways, Emerging Strategies, and Future Directions.
   Tang J, Karbhari N, Campian JL. · · 2025 · cited 31× · PMID 40214448 · DOI 10.3390/cells14070494