Cilengitide in Combination With Irradiation in Children With Diffuse Intrinsic Pontine Glioma
Condition: Diffuse Intrinsic Pontine Glioma
MeSH terms: Glioma; Diffuse Intrinsic Pontine Glioma
Study type: Interventional
Phase: Phase 1

Summary: 
      The aim of the study is to determine the safety of Cilengitide in combination with radiation
      therapy.
    

Detailed description: 
      The prognosis of children and young adults with a malignant glioma in the brain stem or a
      recurrent malignant glioma (in whatever site) is very poor. Over the last few decades, many
      therapeutic trials have been performed but have failed to significantly improve survival in
      these patients. There is thus a need to test new drugs in these indications. There is a
      strong biological rationale for the use of anti-angiogenic drugs in high-grade glioma.
      Cilengitide (EMD121974; Merck KgaA, Darmstadt, Germany), a cyclic pentapeptide containing the
      sequence RGD (cyclo-[Arg-Gly-Asp-Dphe-(NmeVal)]) is a selective antagonist of integrins αvβ3
      and αvβ5, which are strongly involved in tumour angiogenesis. Positive results with
      Cilengitide in preclinical models of glioblastoma, its particularly attractive safety profile
      and its encouraging efficacy in phase I and II studies in adults and children make it a
      potentially effective molecule for the treatment of malignant glioma in children.
      Furthermore, its combination with radiotherapy to be appears synergistic, without any
      apparent increase in toxicity.

      In this study, Cilengitide will be evaluated when concurrently administered with radiotherapy
      as a first-line treatment and then as a maintenance monotherapy in children and young adults
      with malignant brain stem glioma. The main objective will be to determine the maximum
      tolerated dose (MTD) of Cilengitide when administered twice weekly as a 60-minute
      intra-venous infusion.
    

Intervention name(s): Cilengitide dose escalation; Cilengitide; Concomitant radiotherapy; Pharmacokinetic; Pharmacogenetic; Exploratory investigation
Intervention type(s): Drug; Drug; Radiation; Biological; Biological; Biological
Intervention description(s): Cilengitide will be administered intravenously over 60 minutes, twice a week, at a given dose.
The Cilengitide dose (mg/m²/infusion)levels are as follows :
240
480
720
1200
1800; Patients will be treated at the recommended dose in order to confirm the recommended cilengitide dose and to carry out the exploratory investigations; 1.8 Gy per fraction for a total of 54 Gy over 6 weeks, from monday to friday of the first cycle. The radiation will imperatively begin between 3 and 7hours after the end of Cilengitide infusion.; A pharmacokinetic assessment for Cilengitide will be carried for all patients. The pharmacokinetic (PK) samples will be drawn during day 1 and day 2 of the first cycle of treatment.; For every patient 1 blood sample will be taken before study treatment. These blood samples can be made at any hour of the day, and does not require to be taken on an empty stomach. DNA will be extracted in the Laboratory of Pharmacology.Constitutional polymorphisms of genes will be measured before the treatment initiation.; Evaluate the metabolic impact of the treatment with dynamic MRI (diffusion, perfusion, spectro), and with FDG-PETand sestamibi SPECT.
Other intervention name(s): Cilengitidine; cilengitidine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Paediatric oncology; Cilengitide; Glioma