Grade IV AstrocytomaPhase 1FOLAGLINCT01700569
Phase-1 Study of Folinic Acid to Modulate MGMT Gene in Glioblastoma
A Phase 1 study testing Temozolomide, folinic acid at pharmacological dose is the escalated drug and High voltage radiation therapy (linear accelerator) in people with Grade IV Astrocytoma and Glioblastoma, run by Institut Cancerologie de l'Ouest at 4 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Grade IV Astrocytoma, Glioblastoma
- What is being tested?
- Temozolomide, folinic acid at pharmacological dose is the escalated drug and High voltage radiation therapy (linear accelerator)
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 4 sitesFrance
- Study dates
- Jan 2013to 16 Apr 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Operated GBM (complete or near complete resection)
- Un-methylated MGMT gene
Who cannot join
- Non operable GBM
- Methylated MGMT
Trial locations and contacts
4 sites in 1 country.
France4 sites
Institut de Cacerologie de l'ouest - site Paul Papin
Angers, 49055
CHU de Lyon
Bron, 69677
ICO site Gauducheau
Nantes, 44805
CLCC Antoine Lacassagne
Nice, 06189
About this study
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.
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.
Read the 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.
- Conditions
- Grade IV Astrocytoma, Glioblastoma
- Being tested
- Temozolomide, folinic acid at pharmacological dose is the escalated drug, High voltage radiation therapy (linear accelerator)
- Keywords
- high-grade, glioma, epigenetic
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodal, capsule dosage available: 5, 20, 10, 180 and 250 mg
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).
folinic acid at pharmacological dose is the escalated drugDrug
Also called Folinate de Calcium, Lederfoline
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Temozolomide; Drug: folinic acid at pharmacological dose is the escalated drug; Radiation: High voltage radiation therapy (linear accelerator) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Tolerated Dose
maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )
Measured: day 43
Secondary outcomes (1)
MGMT gene re-methylation
MGMT gene re-methylation in tumoral and blood samples
Measured: day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startJan 2013
- Primary completion12 Dec 2019
- Study completion16 Apr 2021
Why it stopped: changing the standard of care
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Grade IV AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Antoine Lacassagne, Hospices Civils de Lyon
- Responsible party
- Sponsor
- Investigators
- Mario CAMPONE, MD, PhD, Principal investigator, Institut Cancerologie de l'Ouest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01700569
- Sponsor's protocol ID
- ICO 2012-02
- Other IDs
- 2012-000774-31
- Acronym
- FOLAGLI
- Status last verified
- May 2021
- First submitted
- 12 Sep 2012
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15758009
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01700569
- Acronym / sponsor ID
- FOLAGLI / ICO 2012-02
- Conditions
- Grade IV Astrocytoma, Glioblastoma
- Keywords
- high-grade, glioma, epigenetic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: changing the standard of care
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Collaborators
- Centre Antoine Lacassagne, Hospices Civils de Lyon
- Study start
- Jan 2013 (actual)
- Primary completion
- 12 Dec 2019 (actual)
- Study completion
- 16 Apr 2021 (actual)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Folinic Acid | Experimental | Drug: Temozolomide, Drug: folinic acid at pharmacological dose is the escalated drug, Radiation: High voltage radiation therapy (linear accelerator)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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Operated GBM (complete or near complete resection)
- Un-methylated MGMT gene
Key exclusion criteria (2 listed)
- Non operable GBM
- Methylated MGMT
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TemozolomideAlso: Temodal, capsule dosage available: 5, 20, 10, 180 and 250 mgAll 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). | Drug | Folinic Acid |
| folinic acid at pharmacological dose is the escalated drugAlso: Folinate de Calcium, Lederfoline | Drug | Folinic Acid |
| 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). | Radiation | Folinic Acid |
Primary outcome
Maximal Tolerated Dose
Time frame: day 43
maximal tolerated dose 3x3 patients inclusion(modified Fibonnacci dose escalation )
1 secondary outcome
MGMT gene re-methylation
Time frame: day 43
Results and safety
The study was stopped early (reason given: changing the standard of care). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Background: PubMed 15758009Stupp 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario CAMPONE, MD, PhD principal investigator
Institut Cancerologie de l'Ouest
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Temozolomide, folinic acid at pharmacological dose is the escalated drug and High voltage radiation therapy (linear accelerator) in people with Grade IV Astrocytoma and Glioblastoma, run by Institut Cancerologie de l'Ouest at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: changing the standard of care). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Tolerated Dose (time frame: day 43). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01700569, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.