Inclusion Criteria:

1. Patients with histologically proven primary Glioblastoma Multiforme (GBM) will be
eligible for this protocol.

2. Patients must show unequivocal evidence for tumor recurrence or progression by MRI
scan within 3 weeks prior to registration after failing prior resection (surgery or
biopsy) and/ or chemo- and/or radiation therapy.

3. Recurring tumors must either be accessible for surgery, or , when not accessible for
surgery meet the following criteria:

1. unifocal

2. midline shift < 0.5 cm

3. no radiological signs of uncal herniation

4. All recurring tumors must be restricted to one hemisphere, without signs of
subependymal spreading.

5. Before start of virus treatment histological analysis of the resected, or biopsied
tumor recurrence must confirm the diagnosis of GBM (based on frozen section).

6. Patients may or may not have had prior chemotherapy.

7. Patients must be able to read and understand the informed consent document and must
sign and date the informed consent. Procedures to obtain such informed consent
should be according to ICH-GCP, the local regulatory requirement and the rules
followed at the institute.

8. Patients must be > 18 and < 75 years old.

9. Patients must have a Karnofsky performance status rating > 70 (Appendix 2).

10. Patients must have recovered from the toxic effects of prior therapy. For example,
they must be at least two weeks after vincristine, 6 weeks after nitrosoureas, 3
weeks after procarbazine or temozolomide administration, and 6 weeks after radiation
therapy.

11. If sexually active, patients must be willing to use barrier contraception for the
duration of the study.

12. Patients must have adequate hepatic, renal and bone marrow function, defined as

- absolute neutrophil count (ANC) > 1,5* 109/L

- platelet count of > 100* 109/L

- ALT (SGPT), AST (SGOT) and Alkaline Phosphatase < 2 times ULN

- total bilirubin <1.5 mg/dL

- creatinine <1.5 times ULN

- urea (BUN) <1.5 times ULN

Exclusion Criteria:

1. Patients with active uncontrolled infection. Upper pulmonary infection and flu-like
signs or presence of adenovirus in pre-operative throat-swab or serum sample as
determined by PCR. All patients must be afebrile (<38.0 C) at the start of therapy

2. Evidence of bleeding diathesis or use of anticoagulant medication.

3. Patients with systemic diseases or other unstable conditions which may be associated
with unacceptable anesthetic/ operative risk and/or which would not allow safe
completion of this study protocol, e.g. uncontrolled seizures.

4. Because of the potential risk of a recombinant virus containing a gene involved in
cellular growth regulation and differentiation which could potentially affect a
developing fetus or growing infant, females who are pregnant, at risk of pregnancy,
or breast feeding a baby during the study period are excluded.

5. Because of the potential risk of serious infection in immune-compromised individuals,
patients known to have HIV infection are excluded.

6. Patients with a known germline deficit in the retinoblastoma gene or its related
pathways.

7. Patients with other primary malignancy than GBM. However, patients with curatively
treated carcinoma-in situ or basal cell carcinoma or patients who have been disease
free for at least 2 years and not using any anti-cancer therapy, are eligible.