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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Institut Cancerologie de l'Ouest
Sponsor:
Collaborator:
Centre Antoine Lacassagne
Information provided by (Responsible Party):
Institut Cancerologie de l'Ouest
ClinicalTrials.gov Identifier:
NCT01700569
First received: September 12, 2012
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Institut Cancerologie de l'Ouest:

Primary Outcome Measures:
  • Maximal Tolerated Dose [ Time Frame: day 43 ] [ Designated as safety issue: Yes ]
    maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )


Secondary Outcome Measures:
  • MGMT gene re-methylation [ Time Frame: day 43 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Overall Survival [ Time Frame: Year 1 ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: January 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Non operable GBM
  • Methylated MGMT
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700569

Contacts
Contact: Francois PEIN, MD +33240679908 francois.pein@ico.unicancer.fr

Locations
France
ICO site Gauducheau Recruiting
Nantes, France, 44805
Contact: Mario Campone, MD, PhD    +33240679900    mario.campone@ico.unicancer.fr   
Principal Investigator: Mario CAMPONE, MD, PhD         
Sub-Investigator: Jean S FRESNEL, MD         
Sponsors and Collaborators
Institut Cancerologie de l'Ouest
Centre Antoine Lacassagne
Investigators
Principal Investigator: Mario CAMPONE, MD, PhD Institut Cancerologie de l'Ouest
  More Information

Publications:
Responsible Party: Institut Cancerologie de l'Ouest
ClinicalTrials.gov Identifier: NCT01700569     History of Changes
Other Study ID Numbers: ICO 2012-02, 2012-000774-31
Study First Received: September 12, 2012
Last Updated: February 5, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Institut Cancerologie de l'Ouest:
high-grade
glioma
epigenetic

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Dacarbazine
Folic Acid
Leucovorin
Levoleucovorin
Temozolomide
Alkylating Agents
Antidotes
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on November 24, 2014