NCT02115074

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

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Centre Oscar Lambret · Academic / Other
• Sex: All
• Age: 6 Years – 21 Years
• Healthy volunteers: Not accepted

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).

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

Interventions

Type	Name	Description
DRUG	Fluvastatine	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.
DRUG	Celebrex	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.

Timeline

• Start date: 2014-06-01
• Primary completion: 2018-11-01
• Completion: 2022-01-01
• First posted: 2014-04-15
• Last updated: 2026-03-18

Locations

8 sites across 1 country: France