Clinical trial · Interventional
Treatment With Azacitidine of Recurrent Gliomas With IDH1/2 Mutation
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Recurrent IDH1/2 Mutated Glioma | Glioma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Azacitidine | Drug | Azacitidine | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Azacitidine
- description
- Azacitidine is administered by sub-cutaneous injection at 75 mg/m2 per day for seven consecutive days every 4 weeks until progression, intolerance or end of the study.
- interventionNames
- Drug: Azacitidine
Primary outcomes (1)
- measure
- Progression-Free Survival at 6 months (PFS-6)
- timeFrame
- at Month 6 after first administration of the drug
- description
- Evaluation of the efficacy based on Radiologic Assessment in Neuro-Oncology (RANO) criteria,
Secondary outcomes (3)
- measure
- Incidence of Treatment-Emergent Adverse Events (safety and tolerability)
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Age \> 18 years * Glioma grade II or III with IDH1 or IDH2 mutation * Recurring after standard treatment, ie radiotherapy and at least one alkylating chemotherapy, or alkylating chemotherapy alone in case of gliomatosis cerebri * For the patients treated by radiotherapy, recurrence occurring more than three months from the end of the radiotherapy or occurring outside the irradiated volume * Karnofsky Performance Status \> 50 * Life expectancy \> 9 months * Suitable laboratory values obtained ≤ 7 days before inclusion visit: * Absolute neutrophil count (ANC) ≥ 1500 /mm3 * Leucocytes ≥ 3,0 x 109/L * Platelet count ≥ 75 000 / mm3 * Hemoglobin \> 9.0 g/dL * Serum GlutamoOxaloacetate Transferase (SGOT) (AST) ≤ 3 x Upper Limit of Normal (ULN) * Serum Glutamate Pyruvate Transaminase (SGPT) (ALT) ≤ 3 x ULN * Creatininemia ≤ 1.5 x ULN * Bicarbonates ≥ 22 mmol/l * Women of child-bearing potential (i.e. women who are pre-menopausal or not surgically sterile) must : * Have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. * Agree to use, and to be able to comply with, effective contraception without interruption, throughout the entire duration study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy. * Male patients : * must agree to use a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment and during 3 months after end of treatment. * are informed about the procedures for preservation of sperm before starting treatment. * Written informed consent dated and signed, prior to any study specific procedures (sampling, treatment and analyses). * Affiliation to the French health insurance (recipient or assign) Exclusion Criteria: * Breast-feeding women * Any evidence of severe or uncontrolled systemic diseases (as judged by the investigator), including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) (Screening for chronic conditions is not required) * Active pulmonary disease or congestive cardiac insufficiency * Malignant hepatic tumor at a later stage * Intracranial hypertension or important deviation of the midline on the MRI * Any investigational agents or study drugs from a previous clinical study (within 30 days before the first dose of study treatment * Any chemotherapy, anticancer immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosourea) before the first dose of study treatment * Any unresolved toxicities (excepted alopecia and lymphopenia), from prior therapy greater than CTCAE grade 1 at the time of inclusion * Known hypersensitivity to Azacitidine or Mannitol (E421), (refer to the Investigator's Brochure) * Patients under curatorship or guardianship
References
Publications (0)
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