Safety and Efficacy Study to Treat Recurrent Grade 4 Malignant Brain Tumors

Inclusion criteria

The patients must fulfill all the following criteria:

• Previous histologically-confirmed diagnosis of primary GBM (glioma grade 4 at time of first diagnosis).
• Histologically-confirmed and MRI diagnosed recurrent or progressive GBM after previous resection (surgical or biopsy) and radiation therapy.
• Medically capable of undergoing the planned surgical gross total resection and the catheter placement.
• Age ≥ 18.
• Karnofsky Performance Status of ≥ 70%.
• Life expectancy of ≥ 3 months.
• Patients must already be taking or begin taking corticosteroids at a stable dose of 4 mg every 6 hours for at least 72 hours prior to catheter placement.
• Patients must be capable of taking, or already taking, anticonvulsant medication.
• Patients must have read, signed, and dated an informed consent according to ICH-GCP, the local regulatory requirement and the rules followed at each institution.

Exclusion criteria

Patients fulfilling any of the following criteria should not be enrolled in the study:

• Previous myelosuppressive chemotherapy within the past 4 weeks of the start of the infusion. Patients who have received more than two chemotherapy regimens (single therapy or combination therapy) are ineligible.
• Any form of brain radiation within 10 weeks of the start of the infusion.
• Previous gamma knife radiosurgery, stereotactic radiosurgery, and/or internal radiotherapy, unless the recurrence/progression is histologically confirmed (fine-needle biopsy).
• Prior intracavitary biologic response modifiers or monoclonal antibodies.
• Uncontrolled seizures.
• Bilateral or multifocal tumors.
• Evidence of cerebral uncal herniation.
• Midline brain shift on MRI scan of > 0.5 cm prior to resection; patients with subfalcine herniation may be enrolled.
• Tumors involving the brainstem or cerebellum.
• Diffuse subependymal or CSF disease.
• Women who are pregnant or breast feeding. All women of child-bearing potential should be excluded unless they have a negative pregnancy test and are using adequate contraceptive measures or are surgically sterile. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing.
• Fertile males not practicing adequate contraception and whose female partners are not using adequate contraceptive protection.
• Prior or concurrent investigational treatment within 30 days of study entry.
• Active infection requiring treatment or having an unexplained febrile illness.
• Systemic diseases or other conditions which may be associated with unacceptable anesthetic/operative risk and/or which would not allow safe completion of this study protocol.
• Prior or concurrent malignancy (curatively treated carcinoma-in-situ or basal cell carcinoma or patients who have been disease free for at least 5 years are eligible).