GliomaPhase 1FLUVABREXNCT02115074
Safety of Fluvastatin-Celebrex Association in Low-grade and High Grade Optico-chiasmatic Gliomas
A Phase 1 study testing Fluvastatine and Celebrex in people with Glioma, run by Centre Oscar Lambret at 8 sites in France.
Trial summary
Optico-chiasmatic gliomas have therapeutic feature since surgical resection plays a secondary role. Unlike other sites, many of these tumors are not amenable to complete resection either because of anatomical location, and sometimes they only can be biopsied. Read more about this study
- Who is it for?
- Ages 6 to 21 years
- Conditions the study is for
- Glioma
- What is being tested?
- Fluvastatine and Celebrex
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 8 sitesFrance
- Study dates
- Jun 2014to Jan 2022
- 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 6 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed recurrent or progressive primary hypothalamic-chiasmatic low grade glioma, and not warranting a biopsy or surgery
- Histologically confirmed recurrent or progressive primary hypothalamic-chiasmatic high grade glioma, or in complete remission after a new exeresis, excepted brainstem gliomas
- Relapsed or refractory disease after at least 1 line adjuvant treatment including radiation therapy, but not surgery
- Measurable lesions according to RANO criteria for the patients with low grade glioma and for the patients with high grade glioma included in RP2D level (Recommended Phase 2 Dose).
- Non-measurable lesions according to RANO criteria for patients with high grade glioma included in the dose escalation step.
- Age > 6 years and < 21 years old
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- Lansky score > 70 or WHO score < 2 (neurological conditions associated with the disease should not be taken into consideration)
- Haematological conditions: ANC > 1000/mm3 and platelets > 75000/mm3
- Creatinine < 1.5 x normal for age or calculated clearance > 70 ml/mn/1.73m2
- Hepatic function: Total bilirubin < 3 N and SGOT and SGPT < 4 N
- Muscle enzymes : CPK < 2 N
- No organ toxicity superior to grade 2 according to NCI-CTCAE v4.0
- No allergy, hypersensibility to one of the compounds of the treatment
- Patients able to swallow capsules
- Life expectancy at least > 6 months for low grade gliomas and > 3 months for high grade gliomas
- Patient affiliated with a health insurance system
- Effective contraception for patients (male and female) with reproductive potential throughout the treatment period
- Written informed consent of patient and/or parents/guardians prior to the study participation
Who cannot join
- Chemotherapy within 21 days before D1 of experimental treatment. This period may be shortened in case of previous chemotherapy with vincristine (2 weeks), or extended in case of targeted therapies (4 weeks), or treatment by nitrosoureas (6 weeks)
- Radiotherapy within 6 months before D1 of experimental treatment
- Peptic ulcer disease, or gastrointestinal bleeding
- Known hypersensitivity to sulfonamides.
- History of asthma, acute rhinitis, nasal polyps, angioedema, urticaria or other allergic-type reactions induced by acetylsalicylic acid or NSAIDs , including COX-2 inhibitors (cyclo-oxygenase- 2)
- Inflammatory bowel disease.
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- Known congestive heart failure (NYHA II- IV)
- Ischemic proven, peripheral and/or history of arterial stroke (including transient ischemic attack)
- Pregnancy or breast feeding woman
- Known allergy to experimental treatment
- Organ toxicity superior to grade 2 according to NCI-CTCAE v4.0
- Active infection
- Pre-existing muscle pathology
- Unsuitable for medical follow-up (geographic, social or mental reasons)
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
CHU Angers
Angers, 49933
Centre Oscar Lambret
Lille, 59020
Centre Léon Bérard
Lyon, 69373
Hôpital pour enfants La Timone
Marseille, 13385
Institut Curie
Paris, 75005
Centre Hospitalier de Strasbourg
Strasbourg, 67098
Centre Hospitalier de Purpan - Hôpital des Enfants
Toulouse, 31026
Centre Hospitalier de Nancy
Vandœuvre-lès-Nancy, 54511
About this study
Official title: Phase I Study of Fluvastatin-Celebrex Association for Optico-chiasmatic Low Grade Gliomas and High Grade Gliomas Localized Outside the Brainstem, Relapsed or Refactory, in Children or Young Adults
Optico-chiasmatic gliomas have therapeutic feature since surgical resection plays a secondary role. Unlike other sites, many of these tumors are not amenable to complete resection either because of anatomical location, and sometimes they only can be biopsied. A substantial number of children will have recurrences following resection or will experience progression following incomplete tumor removal or biopsy.
Celebrex is a Cox-2 inhibitor with anti-angiogenic and anti-tumor properties, while statins are known to increase the sensitivity of gliomas to anti-tumor agents. Their association could be administered for long periods, in the hope of much reduced risk of toxicities.
Read more
This is a national, multicentric, interventional, open-label, non-comparative, and non-randomized phase I study evaluating the maximum tolerated dose of the Fluvastatin in combination with fixed-dose of Celebrex.
This project involves 10 SFCE health centers accustomed to phase I / II studies(Société Française de Lutte contre les Cancers et Leucémies de l'Enfant et de l'Adolescent - French Society for the Fight against Cancer and Leukemia in Children and Adolescents).
Read the detailed description
Dose escalation scheme only concerns Fluvastatin, and is based on a CRML model (Continual Reassessment Method Lilelihood approach). Dose associated with a probability of DLT closest to 25% will be considered as Recommended Phase 2 Dose (RP2D).
Escalation phase :
Patients will be included by cohort of 2. First patient will be included at the first dose level of Fluvastatin (2mg/kg/day). The second patient will be included only after sufficient time to assess the absence of DLT on first patient. In absence of DLT during the first 28-day cycle, dose escalation will be allowed (4, then 6 and 8 mg/kg/day of Fluvastatin).
The second and all subsequent patients will be treated at the dose level which DLT probability is closest to 25%, without skipping step. Intra-patient dose escalation is not allowed. Treatment will be administered until progression, or unacceptable toxicity for one year. A minimum of 21 patients will be included during the 1st step, including a minimum of 6 patients receiving RP2D.
Expansion phase :
At RP2D, the number of subjects will be increased to reach a total of 14 evaluable patients, in order to better characterize RP2D safety. Patients will be included in the expansion phase according CRML model as well, to confirm the recommended dose.
Probabilities of DLT associated with each dose level will be re-estimated by CRML progressively, without the need to suspend inclusions. Results could modify RP2D retained during 1st step (dose reduction or a dose re-escalation).
- Conditions
- Glioma
- Being tested
- Fluvastatine, Celebrex
- Keywords
- Low-grade gliomas, high-grade gliomas, optico-chiasmatic, relapsed, refractory
- Medical subject headings
- Glioma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluvastatineDrug
Escalation dose : Level 1: 2mg/kg/day. Level 2: 4mg/kg/day. Level 3: 6mg/kg/day. Level 4: 8mg/kg/day.
Per os from D1 to D14 of each 28 day cycle.
Number of Cycles: until progression or unacceptable toxicity develops.
CelebrexDrug
Also called Celecoxib
Dose levels : 100 mg twice a day (< 20 kg), 200 mg twice a day (20-50 kg), 400 mg twice a day (> 50 kg)
Per os from D1 to D28 of each 28 day cycle.
Number of Cycles: until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Fluvastatine Celebrex | Experimental | dose escalation for Fluvastatine Receives: Drug: Fluvastatine; Drug: Celebrex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of Fluvastatine combined to a fixed-dose of Celebrex
The MTD is evaluated according to NCI-CTC v4.0 scale, and is defined as follows:
- grade 3 or 4 neutropenia leading to a delay of therapy superior to 7 days
- grade 3 or 4 thrombocytopenia requiring transfusions over a period superior to 7 days
- grade 3 or 4 non-hematologic toxicities, excepted the following events:
- nausea and vomiting despite appropriate symptomatic treatment,
- grade 3 fever, and grade 3 liver toxicity but rapidly reversible,
- grade 3 elevation of creatine phosphokinase (CPK) levels, but rapidly reversible (back <3 X normal within 2 weeks after interruption of treatment)
- Toxicity leading to dose reduction (<75% dose protocol) will also be considered as a DLT, although the grade of toxicity does not in itself justify this classification
Measured: 28 days (at the end of the first cycle)
Secondary outcomes (5)
Adverse events
Safety is assessed according to NCI-CTC v4.0 scale
Measured: During all the treatment period, for up to 1 year
Efficacy in terms of overall survival
Efficacy is measured according to RANO criteria
Measured: From date of registration until the date of death from any cause, assessed up to 2 years
Efficacy in terms of progression-free survival
Efficacy is measured according to RANO criteria.
Measured: After 3, 6, 9 and 12 months of treatment
Potential interactions between the two drugs
The Fluvastatin and Celebrex are dosed on the same sample, then compared with pharmacokinetics data from the literature (when drugs are administered alone). The objective is to explore the interaction between the 2 drugs.
Pharmacokinetic analysis is performed by liquid chromatography coupled to mass spectrometry (LC/MS), with UV detection.
Measured: Pharmacokinetics: 1 blood sample of 1.5 ml is collected during cycle 1 and at day 1 of the second cycle before fluvastatine and celebrex administration.
Best response' s distribution during the treatment
Best response is measured according to RANO criteria.
Measured: After 3, 6, 9 and 12 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2014 (estimated)
- Study startJun 2014
- Primary completionNov 2018
- Study completionJan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Oscar Lambret
- Sponsor type
- University, hospital or other
- Collaborators
- Anticancer Fund, Belgium
- Responsible party
- Sponsor
- Investigators
- Pierre LEBLOND, MD, Study director, Centre Oscar Lambret, Lille, FranceNicolas ANDRE, MD, Study director, Hôpital pour Enfants de " La Timone " AP-HM, Marseille, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02115074
- Sponsor's protocol ID
- FLUVABREX-1208
- Other IDs
- 2013-000213-20
- Acronym
- FLUVABREX
- Status last verified
- Mar 2026
- First submitted
- 26 Mar 2014
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Fluvastatin-Celebrex Association for Optico-chiasmatic Low Grade Gliomas and High Grade Gliomas Localized Outside the Brainstem, Relapsed or Refactory, in Children or Young Adults
- ClinicalTrials.gov ID
- NCT02115074
- Acronym / sponsor ID
- FLUVABREX / FLUVABREX-1208
- Conditions
- Glioma
- Keywords
- Low-grade gliomas, high-grade gliomas, optico-chiasmatic, relapsed, refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Centre Oscar LambretUniversity, hospital or other
- Collaborators
- Anticancer Fund, Belgium
- Study start
- Jun 2014 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Jan 2022 (actual)
- First posted
- 15 Apr 2014 (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.
Optico-chiasmatic gliomas have therapeutic feature since surgical resection plays a secondary role. Unlike other sites, many of these tumors are not amenable to complete resection either because of anatomical location, and sometimes they only can be biopsied. A substantial number of children will have recurrences following resection or will experience progression following incomplete tumor removal or biopsy.
Celebrex is a Cox-2 inhibitor with anti-angiogenic and anti-tumor properties, while statins are known to increase the sensitivity of gliomas to anti-tumor agents. Their association could be administered for long periods, in the hope of much reduced risk of toxicities.
This is a national, multicentric, interventional, open-label, non-comparative, and non-randomized phase I study evaluating the maximum tolerated dose of the Fluvastatin in combination with fixed-dose of Celebrex.
This project involves 10 SFCE health centers accustomed to phase I / II studies(Société Française de Lutte contre les Cancers et Leucémies de l'Enfant et de l'Adolescent - French Society for the Fight against Cancer and Leukemia in Children and Adolescents).
Detailed description
Dose escalation scheme only concerns Fluvastatin, and is based on a CRML model (Continual Reassessment Method Lilelihood approach). Dose associated with a probability of DLT closest to 25% will be considered as Recommended Phase 2 Dose (RP2D).
Escalation phase :
Patients will be included by cohort of 2. First patient will be included at the first dose level of Fluvastatin (2mg/kg/day). The second patient will be included only after sufficient time to assess the absence of DLT on first patient. In absence of DLT during the first 28-day cycle, dose escalation will be allowed (4, then 6 and 8 mg/kg/day of Fluvastatin).
The second and all subsequent patients will be treated at the dose level which DLT probability is closest to 25%, without skipping step. Intra-patient dose escalation is not allowed. Treatment will be administered until progression, or unacceptable toxicity for one year. A minimum of 21 patients will be included during the 1st step, including a minimum of 6 patients receiving RP2D.
Expansion phase :
At RP2D, the number of subjects will be increased to reach a total of 14 evaluable patients, in order to better characterize RP2D safety. Patients will be included in the expansion phase according CRML model as well, to confirm the recommended dose.
Probabilities of DLT associated with each dose level will be re-estimated by CRML progressively, without the need to suspend inclusions. Results could modify RP2D retained during 1st step (dose reduction or a dose re-escalation).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fluvastatine Celebrex | Experimental | Drug: Fluvastatine, Drug: Celebrexdose escalation for Fluvastatine |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- Histologically confirmed recurrent or progressive primary hypothalamic-chiasmatic low grade glioma, and not warranting a biopsy or surgery
- Histologically confirmed recurrent or progressive primary hypothalamic-chiasmatic high grade glioma, or in complete remission after a new exeresis, excepted brainstem gliomas
- Relapsed or refractory disease after at least 1 line adjuvant treatment including radiation therapy, but not surgery
- Measurable lesions according to RANO criteria for the patients with low grade glioma and for the patients with high grade glioma included in RP2D level (Recommended Phase 2 Dose).
- Non-measurable lesions according to RANO criteria for patients with high grade glioma included in the dose escalation step.
Key exclusion criteria (14 listed)
- Chemotherapy within 21 days before D1 of experimental treatment. This period may be shortened in case of previous chemotherapy with vincristine (2 weeks), or extended in case of targeted therapies (4 weeks), or treatment by nitrosoureas (6 weeks)
- Radiotherapy within 6 months before D1 of experimental treatment
- Peptic ulcer disease, or gastrointestinal bleeding
- Known hypersensitivity to sulfonamides.
- History of asthma, acute rhinitis, nasal polyps, angioedema, urticaria or other allergic-type reactions induced by acetylsalicylic acid or NSAIDs , including COX-2 inhibitors (cyclo-oxygenase- 2)
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 |
|---|---|---|
| FluvastatineEscalation dose : Level 1: 2mg/kg/day. Level 2: 4mg/kg/day. Level 3: 6mg/kg/day. Level 4: 8mg/kg/day. Per os from D1 to D14 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | Fluvastatine Celebrex |
| CelebrexAlso: CelecoxibDose levels : 100 mg twice a day (< 20 kg), 200 mg twice a day (20-50 kg), 400 mg twice a day (> 50 kg) Per os from D1 to D28 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | Fluvastatine Celebrex |
Primary outcome
Maximum tolerated dose (MTD) of Fluvastatine combined to a fixed-dose of Celebrex
Time frame: 28 days (at the end of the first cycle)
The MTD is evaluated according to NCI-CTC v4.0 scale, and is defined as follows: * grade 3 or 4 neutropenia leading to a delay of therapy superior to 7 days * grade 3 or 4 thrombocytopenia requiring transfusions over a period superior to 7 days * grade 3 or 4 non-hematologic toxicities, excepted the following events: * nausea and vomiting despite appropriate symptomatic treatment, * grade 3 fever, and grade 3 liver toxicity but rapidly reversible, * grade 3 elevation of creatine phosphokinase (CPK) levels, but rapidly reversible (back <3 X normal within 2 weeks after interruption of treatment) * Toxicity leading to dose reduction (<75% dose protocol) will also be considered as a DLT, although the grade of toxicity does not in itself justify this classification
5 secondary outcomes
Adverse events
Time frame: During all the treatment period, for up to 1 year
Efficacy in terms of overall survival
Time frame: From date of registration until the date of death from any cause, assessed up to 2 years
Efficacy in terms of progression-free survival
Time frame: After 3, 6, 9 and 12 months of treatment
Potential interactions between the two drugs
Time frame: Pharmacokinetics: 1 blood sample of 1.5 ml is collected during cycle 1 and at day 1 of the second cycle before fluvastatine and celebrex administration.
Best response' s distribution during the treatment
Time frame: After 3, 6, 9 and 12 months of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Individual participant dataSharing planned: No
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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.
Pierre LEBLOND, MD study director
Centre Oscar Lambret, Lille, France
Nicolas ANDRE, MD study director
Hôpital pour Enfants de " La Timone " AP-HM, Marseille, France
8 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 Fluvastatine and Celebrex in people with Glioma, run by Centre Oscar Lambret at 8 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 18 inclusion and 14 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: finished, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) of Fluvastatine combined to a fixed-dose of Celebrex (time frame: 28 days (at the end of the first cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Mar 2026.