E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed diffuse intrinsic pontine glioma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006143 |
E.1.2 | Term | Brain stem glioma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- 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 |
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E.2.2 | Secondary objectives of the trial |
- 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
- MTD during the first 6 weeks of study treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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the study will end when each of the following is fulfilled: • The last subject received the last dose of study medication (including a safety follow-up of 28 days). • The study objectives could be answered, i.e. the dose ranging exercise was completed, the additional 20 patients in the cohort extension were treated and the final analysis on the secondary endpoints was performed.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |