Phase I Trial of Intratumoral Injection of DTI-015 for Recurrent Malignant Gliomas

Inclusion Criteria:

- Histologic proof of recurrent previously irradiated supratentorial malignant gliomas
including anaplastic astrocytoma, glioblastoma multiforme, anaplastic
oligodendroglioma, or anaplastic ependymoma.

- It must be judged that gross total resection of the patient's tumor is not possible
or the patient must refuse open resection of tumor. The decision that the tumor
cannot be totally resected will be made by and mutually agreed upon by the physician
investigators in the study.

- There must be a tumor volume of each tumor component greater than or equal to 0.5 and
less than or equal to 15 cubic centimeters.

- The patient must be undergoing a stereotactic biopsy for other clinical reasons than
the injection of DTI-015.

- The patient must have a Karnofsky functional status rating greater than or equal to
60.

- The patient must be fully recovered from the acute effects of any prior chemotherapy
or radiotherapy.

- The patient must be able to read and fully understand the informed consent document
and must sign the informed consent indicating that they are aware of the
investigational nature of this study in keeping with the policies of this hospital.

- The patient must be willing and able to comply with the protocol.

- For a female patient of childbearing potential, the patient must not be pregnant as
evidenced by a menses in the last 8 weeks or by a negative urine HCG pregnancy test.

Exclusion Criteria:

- Any radiotherapy or chemotherapy during four weeks prior to entering the study.

- Nitrosoureas or mitomycin C during six weeks prior to entering the study.

- Patients with active uncontrolled infection.

- Serious liver or bone marrow disorder - specifically serum bilirubin >2.0 mg%, SGOT
>2.5 times normal, SGPT >2.5 times normal, absolute neutrophil count <1500/mm3,
platelet count <100,000/mm3.

- Evidence of renal failure (blood creatinine >2.0 mg%, BUN >30 mg/dl or creatinine
clearance >40 ml/min

- Evidence of a bleeding diathesis or use of anticoagulant medications.

- Unstable or severe intercurrent medical conditions.

- For females: risk of pregnancy (i.e., unwillingness to use adequate protection to
prevent pregnancy), breast feeding a baby during the study period, or lactation.

- Tumors shaped into 3 or more components are excluded. Ovoid-shaped or spherical
tumors are allowed. Central necrosis and/or central cystic areas are allowed as long
as there is an enhancing rim with a thickness >5 mm.

- Patients who have undergone a partial resection of tumor and who have a cavity inside
the residual tumor are excluded.

- Patients with tumors located in the following areas of the brain will be excluded:
brainstem (pons or medulla), midbrain (mesencephalon), primary sensorimotor cortex in
the dominant hemisphere, or within 1.5 cm of the optic chiasm, either optic nerve, or
any other cranial nerve.

- Patients with tumors extending into the ventricular system will also be excluded.