Safety of Fluvastatin-Celebrex Association in Low-grade and High Grade Optico-chiasmatic Gliomas

NCT02115074 | Completed Phase 1 DMC

• 2 other identifiers: FLUVABREX-12082013-000213-20
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

Brief 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. 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).

Conditions

Glioma

Keywords

Low-grade gliomas; high-grade gliomas; optico-chiasmatic; relapsed; refractory

Outcome Measures

Primary Outcomes (1)

• 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

  28 days (at the end of the first cycle)

Secondary Outcomes (5)

• Adverse events

  During all the treatment period, for up to 1 year

• Efficacy in terms of overall survival

  From date of registration until the date of death from any cause, assessed up to 2 years

• Efficacy in terms of progression-free survival

  After 3, 6, 9 and 12 months of treatment

• Potential interactions between the two drugs

  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

  After 3, 6, 9 and 12 months of treatment

Study Arms (1)

Fluvastatine Celebrex

EXPERIMENTAL

dose escalation for Fluvastatine

Drug: Fluvastatine; Drug: Celebrex

Interventions

Fluvastatine DRUG

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.

Fluvastatine Celebrex

Celebrex DRUG

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.

Also known as: Celecoxib

Fluvastatine Celebrex

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Centre Oscar Lambret: lead
• Anticancer Fund, Belgium: collaborator

Study Sites (8)

CHU Angers

Angers, 49933, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Hôpital pour enfants La Timone

Marseille, 13385, France

Location

Institut Curie

Paris, 75005, France

Location

Centre Hospitalier de Strasbourg

Strasbourg, 67098, France

Location

Centre Hospitalier de Purpan - Hôpital des Enfants

Toulouse, 31026, France

Location

Centre Hospitalier de Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Glioma; Recurrence

Interventions

Fluvastatin; Celecoxib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Pierre LEBLOND, MD

  Centre Oscar Lambret, Lille, France

  STUDY DIRECTOR

• Nicolas ANDRE, MD

  Hôpital pour Enfants de " La Timone " AP-HM, Marseille, France

  STUDY DIRECTOR

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: March 26, 2014
• First Posted: April 15, 2014
• Study Start: June 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: January 1, 2022
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)