Inclusion Criteria

Inclusion criteria

- Written informed consent

- Histological verification of primary GBM and failure after radiotherapy and TMZ

- Previously received radiotherapy and TMZ

- More than 4 weeks since any of the following prior treatments

- Chemotherapy (6 weeks for nitrosureas or mitomycin C)

- Radiotherapy to nontarget lesions or lesions that are not to be biopsied

- Investigational agents

- More than 6 months since prior major surgery or open biopsy and recovered (only 6
weeks required if operation is for recurrent BGM)

- ● ECOG performance status 0-1

- Age > 18 years

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Fertile females must use anticonception (p- pills, IUD, depot injection of gestagen,
subdermal

- implantation, hormonal vaginal ring or transdermal depot plaster, throughout the
study and 3

- months after discontinuation of study drugs. Fertile men must use dobbelt barrier
method

- (preservative with sperm inhibiting creme) or female partner uses the above mentioned

- contraception.

- Fertile males must use preservatives.

Exclusions criteria

- Prior treatment with BIBF 1120 or any other VEGFR inhibitor, except bevacizumab in
Group 2

- Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or
therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the
past 4 weeks prior to treatment with the trial drug.

- Persistence of clinically relevant therapy related toxicity from previous chemo
and/or radiotherapy

- Treatment with other investigational drugs or treatment in another clinical trial
within the past 4 weeks before start of therapy or concomitantly with the trial

- Therapeutic anticoagulation( except low-dose heparin and/or heparin flush as needed
for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy
(except for low-dose therapy with acetylsalicylic acid<325mg per day

- Major injuries within the past 10 days prior to start of study treatment with
incomplete wound healing and/or planned surgery during the on-treatment study period

- History of clinically significant haemorrhagic or thromboembolic event in the past 6
months

- Known inherited predisposition to bleeding or thrombosis

- Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable
angina, history of infarction within the past 12 months prior to start of study
treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia,
pericardial effusion)

- Proteinuria CTCAE grade 2 or greater

- Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN

- Coagulation parameters: International normalised ratio ( INR) > 2, prothrombin time

- (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN

- Absolute neutrophil count ( ANC) < 1500/ml, platelets < 100000/ml, Haemoglobin <
9.0 g/dl

- Other malignancies within the past 5 years other then basal cell skin cancer or
carcinoma in situ of the cervix

- Active serious infections in particular if requiring systemic antibiotic or
antimicrobial therapy

- Active or chronic hepatitis C and/or B infection

- Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug

- Serious illness or concomitant non-oncological disease such as neurologic,
psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or
laboratory abnormality that may increase the risk associated with study participation
or study drug administration and in the judgment of the investigator would make the
patient inappropriate for entry into the study.

- Pregnancy or breast feeding

- Psychological, familial, sociological or geographical factors potentially hampering
compliance with the study protocol and follow-up schedule

- active alcohol or drug abuse