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.

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01700569

Acronym

FOLAGLI

Enrollment

Registered

2012-10-04

Start date

2013-01-31

Completion date

2021-04-16

Last updated

2023-02-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Glioblastoma, Grade IV Astrocytoma

Keywords

high-grade, glioma, epigenetic

Brief summary

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.

Detailed description

Glioblastoma treated by Stupp regimen (Temozolomide + radiation therapy) have a different outcome depending on the methylation status of MGMT gene: when the gene is unmethylated, the repair process is active and the prognostic poor. In pre-clinical models, it has been demonstrated that Folic acid could re-methylate the MGMT gene and therefore the repair process to radiation and temozolomide could be limited, allowing a better prognosis. The proposed phase-1 study will explore the safety and efficacy of escalated doses of oral Folinic acid concomitantly with Stupp regimen. To determine the MTD is the main objective of the study, then the toxicty profile, the RDP2 and the methylation process efficacy at the MGMT gene level.

Interventions

DRUGTemozolomide

All the Patients are treated by oral Temozolomide 75 mg/m²/day every day during 42 days, 30 minutes after Folinic acid and 120 min before the radiation dose to the brain tumor. After one month rest, the maintenance phase consists of:Temozolomide is given orally (30 min after Folinic acid), at 200 mg/m²/day every day during 5 days: one course every month during 6 months (6 maintenance course).

DRUGfolinic acid at pharmacological dose is the escalated drug

RADIATIONHigh voltage radiation therapy (linear accelerator)

Brain tumor field is irradiated Five days a week, during Stupp regimen during 6 weeks. During the sams time, Folinic acid and Temozolomide are given orally every days (six weeks).

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Operated GBM (complete or near complete resection) * Un-methylated MGMT gene

Exclusion criteria

* Non operable GBM * Methylated MGMT

Design outcomes

Primary

Measure	Time frame	Description
Maximal Tolerated Dose	day 43	maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )

Secondary

Measure	Time frame	Description
MGMT gene re-methylation	day 43	MGMT gene re-methylation in tumoral and blood samples

Other

Measure	Time frame	Description
Progression-free survival (PFS)	Year 1	Progression-free survival (PFS)
Folic acid and Temozolomide combination Toxicity evaluation	day 43	Acute toxicity: Common toxicity criteria version 4.03

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026