Phase-1 Study of Folinic Acid to Modulate MGMT Gene in Glioblastoma (FOLAGLI)

February 20, 2023 updated by: Institut Cancerologie de l'Ouest

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.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49055
        • Institut de Cacerologie de l'ouest - site Paul Papin
      • Bron, France, 69677
        • CHU de Lyon
      • Nantes, France, 44805
        • ICO site Gauducheau
      • Nice, France, 06189
        • CLCC Antoine Lacassagne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • Non operable GBM
  • Methylated MGMT

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Folinic Acid
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.
Drug: Temozolomide
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).
Other Names:
  • Temodal
  • capsule dosage available: 5, 20, 10, 180 and 250 mg
Drug: folinic acid at pharmacological dose is the escalated drug
Other Names:
  • Folinate de Calcium, Lederfoline
Radiation: High 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).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MGMT gene re-methylation
Time Frame: day 43
MGMT gene re-methylation in tumoral and blood samples
day 43

Other Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Cancerologie de l'Ouest

Collaborators

Hospices Civils de Lyon
Centre Antoine Lacassagne

Investigators

  • Principal Investigator: Mario CAMPONE, MD, PhD, Institut Cancerologie de l'Ouest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2013

Primary Completion (Actual)

December 12, 2019

Study Completion (Actual)

April 16, 2021

Study Registration Dates

First Submitted

September 12, 2012

First Submitted That Met QC Criteria

October 2, 2012

First Posted (Estimate)

October 4, 2012

Study Record Updates

Last Update Posted (Estimate)

February 21, 2023

Last Update Submitted That Met QC Criteria

February 20, 2023

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICO 2012-02
  • 2012-000774-31 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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