Newly diagnosed diffuse intrinsic pontine glioma MedDRA version: 12.1 Level: LLT Classification code 10006143 Term: Brain stem glioma
Conditions
Interventions
Product Name: Cilengitide
Product Code: EMD 121974
Pharmaceutical Form: Solution for infusion
CAS Number: 188968-51-6
Current Sponsor code: EMD121974
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Centre Oscar Lambret
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed diffuse intrinsic pontine glioma (grade II, III and IV WHO) - Metastatic disease allowed - MRI measurable disease according to the WHO criteria and for extension cohort: Patient is able to undergo functional MRI (diffusion, perfusion, spectro) Patient is able to undergo FDG-PET and sestamibi SPECT - Life expectancy > 8 weeks after the start of study treatment. - No prior chemotherapy for the present cancer; no treatment for any other cancer during the last 5 years - No prior cerebral radiation therapy - Age > 6 months and = 21 years - Lansky Play Scale = 50 or ECOG Performance Status = 2; NB: Children with a worse performance status due to glioma-related motor paresis can be included. - Absolute neutrophils count = 1500, Platelets = 100 000 - Total bilirubin = 1,5 x ULN, AST and ALT = 2,5 x ULN - Serum creatinine = 1,5 X ULN for age. If serum creatinine = 1,5 ULN, creatinine clearance must be = 70 ml/min/1.73 m² (EDTA radioisotope GFR or 24 hours urines collection) - Normal coagulation tests : prothrombin rate (prothrombin time = PT), TCA (PTT), fibrinogen - No current organ toxicity = grade 2 according to the NCI-CTCAE version 4.0 - If anticonvulsants are currently administered, the dosing regimen must be stable within 1 week prior to the first dose of Cilengitide - If corticosteroids are admininstered, the dosing regimen must be stable = 5 days prior to the first dose of Cilengitide. - Effective contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the last administration of Cilengitide. - Negative pregnancy test (serum beta-HCG) within 1 week prio to start of study treatment in females of reproductive potential - Patient covered by government health insurance - Written informed consent given by patient and/or parents/ guardians prior to the study participation Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Inclusion criteria failure - History of coagulation disorder associated with bleeding or recurrent thrombotic events. - Prior anti-angiogenic therapy - Any other concomitant anti-cancer treatment not foreseen by this protocol. - Concomitant inclusion in another therapeutic clinical trial; participation in another therapeutic clinical trial during the last 30 days. - Pregnancy or breast feeding woman - Uncontrolled intercurrent illness or active infection - Unable for medical follow-up (geographic, social or mental reasons)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To determine the Maximal Tolerated Dose (MTD) of Cilengitide, administered intravenously over 60 minutes, twice a week, in children and young adults with newly diagnosed diffuse intrinsic pontine glioma, in combination with radiation therapy;Secondary Objective: - To describe the safety profile of Cilengitide - To study the pharmacokinetic parameters of Cilengitide - To estimate efficacy in terms of response according to histopathology - To estimate progression-free and overall survival. Exploratory investigations : For all patients: - To confirm the histological diagnosis on paraffin tumor sample - To determine on frozen tumor sample: the expression levels of angiogenic factors like integrins, endothelial growth factors, vascular marker for the determination of the microvascular density, matrix proteins, some factors of the signaling pathways, and apoptotic factors the gene profils in populations of response/non-response patients (CGH-array) - To study pharmacogenetic parameters and their correlation with prediction of treatment response on constitutional DNA For cohort extension: - To evaluate the metabolic impact of the treatment with dyna-mic MRI (diffusion, perfusion, spectro), and with FDG-PET and sestamibi SPECT.;Primary end point(s): - MTD during the first 6 weeks of study treatment | — |
Countries
France
Outcome results
None listed