Cilengitide in Combination With Irradiation in Children With Diffuse Intrinsic Pontine Glioma

Inclusion Criteria

• •Histologically confirmed diffuse intrinsic pontine glioma
• •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 and young adults with a worse performance status due to glioma-related motor paresis can be included.
• •Absolute neutrophils count \> 1.5 x 109/l, Platelets \> 100 x 109/l
• •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 NCICTCAE version 4.0, especially cardiovascular or renal disease (nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment). In case of known or possible cardiac disease, a cardiological advice will be required prior to the inclusion in the study
• •If anticonvulsants are currently administered, the dosing regimen must be stable within 1 week prior to the first dose of Cilengitide
• •If corticosteroids are administered, 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 prior 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
• •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)