NCT01700569

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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jan 2013

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 12, 2012

Completed
22 days until next milestone

First Posted

Study publicly available on registry

October 4, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

January 1, 2013

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 12, 2019

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 16, 2021

Completed
Last Updated

February 21, 2023

Status Verified

May 1, 2021

Enrollment Period

6.9 years

First QC Date

September 12, 2012

Last Update Submit

February 20, 2023

Conditions

Grade IV AstrocytomaGlioblastoma

Keywords

high-gradegliomaepigenetic

Outcome Measures

Primary Outcomes (1)

  • Maximal Tolerated Dose

    maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )

    day 43

Secondary Outcomes (1)

  • MGMT gene re-methylation

    day 43

Other Outcomes (2)

  • Progression-free survival (PFS)

    Year 1

  • Folic acid and Temozolomide combination Toxicity evaluation

    day 43

Study Arms (1)

Folinic Acid

EXPERIMENTAL

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: TemozolomideDrug: folinic acid at pharmacological dose is the escalated drugRadiation: High voltage radiation therapy (linear accelerator)

Interventions

TemozolomideDRUG

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).

Also known as: Temodal, capsule dosage available: 5, 20, 10, 180 and 250 mg
Folinic Acid
folinic acid at pharmacological dose is the escalated drugDRUG
Also known as: Folinate de Calcium, Lederfoline
Folinic Acid
High voltage radiation therapy (linear accelerator)RADIATION

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).

Folinic Acid

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Non operable GBM
  • Methylated MGMT

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Institut de Cacerologie de l'ouest - site Paul Papin

Angers, 49055, France

Location

CHU de Lyon

Bron, 69677, France

Location

ICO site Gauducheau

Nantes, 44805, France

Location

CLCC Antoine Lacassagne

Nice, 06189, France

Location

Related Publications (1)

  • Stupp 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: 15758009BACKGROUND

MeSH Terms

Conditions

GlioblastomaGlioma

Interventions

TemozolomideParticle Accelerators

Condition Hierarchy (Ancestors)

AstrocytomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

DacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsRadiation Equipment and SuppliesEquipment and Supplies

Study Officials

  • Mario CAMPONE, MD, PhD

    Institut Cancerologie de l'Ouest

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2012

First Posted

October 4, 2012

Study Start

January 1, 2013

Primary Completion

December 12, 2019

Study Completion

April 16, 2021

Last Updated

February 21, 2023

Record last verified: 2021-05

Locations

FR(4)