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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01700569
Recruitment Status : Unknown
Verified August 2016 by Institut Cancerologie de l'Ouest.
Recruitment status was:  Recruiting
First Posted : October 4, 2012
Last Update Posted : August 31, 2016
Centre Antoine Lacassagne
Information provided by (Responsible Party):
Institut Cancerologie de l'Ouest

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.

Condition or disease Intervention/treatment Phase
Grade IV Astrocytoma Glioblastoma Drug: Temozolomide Drug: folinic acid at pharmacological dose is the escalated drug Radiation: High voltage radiation therapy (linear accelerator) Phase 1

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  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : January 2013
Estimated Primary Completion Date : March 2017
Estimated Study Completion Date : March 2018

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 Name: 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).

Primary Outcome Measures :
  1. Maximal Tolerated Dose [ Time Frame: day 43 ]
    maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )

Secondary Outcome Measures :
  1. MGMT gene re-methylation [ Time Frame: day 43 ]

Other Outcome Measures:
  1. Overall Survival [ Time Frame: Year 1 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

Exclusion Criteria:

  • Non operable GBM
  • Methylated MGMT

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01700569

Contact: Francois PEIN, MD +33240679908

ICO site Gauducheau Recruiting
Nantes, France, 44805
Contact: Mario Campone, MD, PhD    +33240679900   
Principal Investigator: Mario CAMPONE, MD, PhD         
Sub-Investigator: Jean S FRESNEL, MD         
Sponsors and Collaborators
Institut Cancerologie de l'Ouest
Centre Antoine Lacassagne
Principal Investigator: Mario CAMPONE, MD, PhD Institut Cancerologie de l'Ouest

Responsible Party: Institut Cancerologie de l'Ouest Identifier: NCT01700569     History of Changes
Other Study ID Numbers: ICO 2012-02
2012-000774-31 ( EudraCT Number )
First Posted: October 4, 2012    Key Record Dates
Last Update Posted: August 31, 2016
Last Verified: August 2016

Keywords provided by Institut Cancerologie de l'Ouest:

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Folic Acid
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances