Inclusion Criteria:

• Patients present with a first recurrence or first progression of a histological confirmed primary supratentorial glioblastoma multiforme WHO Grade IV (Classification following WHO criteria).
• Patients with surgical resection of first tumor progression: Following standard therapy patients must have evidence of first tumor progression. In general, patients may have undergone prior surgical resection of the first tumor progression and will be eligible if the following conditions apply:
• Patients must have recovered from the effects of surgery
• To adequately asses the GBM before surgery and the extent of residual disease postoperatively, two MRIs scans have to be performed:
• The first MRI scan within 2 weeks before surgery to document a progressed or recurrent GBM. The second MRI scan within 48 hours after surgery.
• Patients without surgical resection of first tumor progression:
• Patients must have evidence of first tumor progression following standard therapy as measured by a baseline MRI within 2 weeks prior to study enrollment (Macdonald criteria: i.e. tumor growth > 25% or new lesion).
• Resolution of all acute toxic effects of prior therapy to grade ≤ 1 (except alopecia)
• Patients must have an ECOG performance status of 0-2
• Patients must be ≥ 18 years and ≤ 75 years of age, with a life expectancy of greater than 8 weeks
• Patients must have adequate organ function as defined by the following criteria:

Bone Marrow Reserve - Platelets ≥ 75.000/μL

• Absolute Neutrophil Count (ANC) ≥ 1500/μL
• Hemoglobin ≥ 10.0 g/dL Blood Coagulation - aPTT ≤ 1.5 times upper limit of normal (ULN) Hepatic Function - ASAT and ALAT ≤ 1.5 times ULN
• ALP ≤ 2.5 times ULN
• Total Serum Bilirubin < 1 times ULN Renal Function - Serum Creatinine ≤ 1.5 times ULN Metabolism - Serum Albumin ≥ 3.0 g/dL Heart Function - Left Ventricular Ejection Fraction (LVEF) ≥ 50% as measured by transthoracic echocardiogram ECHO) All tests must be performed ≤ 3 days prior to study enrollment. Eligibility for hemoglobin count may be reached by transfusion
• Signed and dated informed consent document by the patient, indicating that the patient has been informed of all the pertinent aspects of the trial prior to study enrollment
• Willingness and ability of the patient to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

• The patient is active participant in another clinical trial.

• Exclusion of patients in the event of

  • surgery for recurrence/progression within 1 week prior to study enrollment
  • chemotherapy within 4 weeks prior to study enrollment
  • treatment with more than one chemotherapy regime
  • radiation therapy within 8 weeks to study enrollment
  • evidence in baseline MRI of intratumoral or peritumoral hemorrhage deemed clinically significant by the treating physician (area of hemorrhage > 25% of tumor area)

• Significant Co-Morbidities within 12 months prior to study enrollment

  • myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure
  • pulmonary embolus
  • cerebro-vascular accident including TIA (transient ischemic attack)

• Significant Co-Morbidities at Baseline Evaluation

  • Clinically significant ongoing cardiac dysrhythmias of grade ≥ 2, atrial fibrillation of any grade, QTc interval > 470 ms measured by electrocardiogram (ECG)
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
  • A known HIV (human immunodeficiency virus) or Hepatitis B/C infection or severe acute infection
• Anticoagulation: Current treatment with therapeutic doses of Marcoumar / Sintrom excluding thrombosis prophylaxis with low dose Heparin.
• Antiepileptic Drugs: Concurrent use of EIADs within 2 weeks of study enrollment (patients must discontinue EIAD treatment ≥ 14 days prior to study enrollment)

• Pregnancy, Breastfeeding and Non-Contraception

  • Female patients who are pregnant or nursing
  • Patients who are sexually active and unwilling or unable to use a medically acceptable method of contraception during the trial.

• Evidence of increased intracranial pressure

  • midline shift > 5 mm
  • distinct nausea and vomiting
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would impart excess risk associated with study participation or study drug administration, or which would make the patient inappropriate for entry into this study. The decision to enroll the patient in this study is in the judgment of the investigator.