Clinical trial · Interventional
Phase-1 Study of Folinic Acid to Modulate MGMT Gene in Glioblastoma
Phase I Study of Escalated Pharmacologic Dose, of Oral Folinic Acid in Combination With Temozolomide, According to Stupp R. Regimen, in Patients With Operated Grade-IV Astocytoma and a Non-methylated Gene Status of MGMT.
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): changing the standard of care
Summary
Brief summary (as posted)
O6-méthylguanine méthyltransférase (MGMT) is the main repair gene after DNA lesion induced by Temozolomide in combination with radiation therapy of Glioblastoma (GBM) in Stupp.R et al published regimen. In preclinical models, it has been demonstrated that MGMT methylation (which is silencing the DNA repair process) is achievable by folic acid. About half of the patients with operated GBM have an un-methylated MGMT gene status and therefore a poorer prognosis. A phase-1 dose escalation study is proposed with pharmacologic doses of folinic acid in combination with temozolomide and radiotherapy of operated GBM.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
| Grade IV Astrocytoma | — | UNRESOLVED | — |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| folinic acid at pharmacological dose is the escalated drug | Drug | — | UNRESOLVED |
| High voltage radiation therapy (linear accelerator) | Radiation | — | UNRESOLVED |
| Temozolomide | Drug | Temozolomide | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Folinic Acid
- description
- Folinic acid is given orally every day during the radiation therapy (47 days), then 5 days at each of the 6 maintenance cycle of temozolomide. The dose is escalated in a "3x3" method and the levels are: 5mg, 10mg, 15mg, 30mg, 60mg.
- interventionNames
- Drug: Temozolomide
- Drug: folinic acid at pharmacological dose is the escalated drug
- Radiation: High voltage radiation therapy (linear accelerator)
Primary outcomes (1)
- measure
- Maximal Tolerated Dose
- timeFrame
- day 43
- description
- maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )
Secondary outcomes (1)
- measure
- MGMT gene re-methylation
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 70 Years
Show eligibility criteria text
Inclusion Criteria: * Operated GBM (complete or near complete resection) * Un-methylated MGMT gene Exclusion Criteria: * Non operable GBM * Methylated MGMT
References
Publications (1)
- BACKGROUNDStupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. PMID 15758009