Cilengitide and Metronomic Temozolomide for Relapsed or Refractory High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas in Children and Adolescents

Inclusion Criteria:

1. Diagnosis of high-grade malignant glioma confirmed by central neuropathological review (last MRI diagnosis not older than 4 weeks) - including glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (analogous to WHO III), giant cell glioblastoma (WHO IV), and gliosarcoma (WHO IV) - or diagnosis of diffuse intrinsic pontine glioma confirmed by central neuroradiological review - refractory to standard treatment, or relapsed or progressive after first-line therapy.
2. Patient aged 3 years and older but under 18 years at time of relapse diagnosis
3. Written informed consent of the patient (mandatory from 15 years of age) or the parents (mandatory till 18 years of age).

Exclusion Criteria:

1. Known hypersensitivity or contraindication to any study drugs
2. Other (simultaneous) malignancies
3. Pregnancy and / or lactation
4. Patients who are sexually active refusing to use effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile)
5. Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
6. Severe concomitant diseases (e.g. immune deficiency syndrome) or HIV infection
7. Severe psychological disease or neurological damage without possibility to communicate
8. Clinical signs of intracranial pressure
9. Intracerebral hemorrhage or history of intracerebral hemorrhage
10. Requirements for laboratory test results not older than 2 weeks before patient´s inclusion:

    Platelets \< 100 000/µl (\< 100 Gpt/l) PT, INR and PTT above normal range Absulute neutrophil count ≤ 1 500/µl (\< 1,5 Gpt/l) Hemoglobin \< 10g/dl (\< 6,4 mmol/L) Serum creatinine ≥ 1,5 x upper limit of normal range or creatinine clearance rate ≤ 60 ml/min/m2 (corrected for body surface area) Total bilirubin ≥ 1,5 x upper limit of normal range SGOT (ASAT) and SGPT (ALAT) ≥ 2,5 x upper limit of normal range Alkaline phosphatase ≥ 2,5 x upper limit of normal range
11. Hereditary Intrinsic Platelet Disorders
12. Ongoing irradiation or chemotherapy (within the last 4 weeks)
13. Estimated life expectancy of less than 2 months