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

This study will involve 45 patients with malignant glioma brain tumors. Before the study, all
patients will be given a physical exam and blood and urine tests, and they will be asked
about their cancer and treatment. A magnetic resonance imaging (MRI) scan of the brain will
pinpoint the location of the tumor. Female patients who are able to have children will have a
pregnancy test. All patients will be asked about their quality of life and will undergo tests
of their mental functions. Patients might receive a steroid drug for several days before and
after the treatment. This will help prevent swelling around the tumor. Patients will also be
given a drug to prevent convulsions.

DTI-015 will be injected through a catheter (a hollow tube) into the center of the brain
tumor. For patients undergoing a needle biopsy, computer ("stereotactic") guidance will be
used to place the catheter. For patients undergoing an open brain operation, the catheter
will be placed under the direct vision of the surgeon or with computer guidance. It is
possible that the injection might not be done in the brain operation patients because there
either is too much or too little tumor after the resection. The catheter will be removed
after the injection.

Each patient will receive only one injection although one of the first three patients might
receive a second injection if the first injection volume was less than 25% of the tumor
volume. A second injection can also be given to those patients who were stable after the
first injection and develop a nodule of growth. If >250 mg BCNU total was injected, any
repeat injection cannot be done for at least 6 weeks. The dose of DTI-015 will depend on the
size of the patient's tumor. The dose level will be increased after the first 3 patients and
again after the next 3 patients. After the treatment, the patient will remain in the hospital
for 1 day.

Several tests will be repeated during the study. Patients will come to M.D. Anderson every
2-4 weeks for a total of 12 weeks. Blood tests will be done during each visit. An MRI scan of
the brain will be done every month for 3 months. The physical exam, quality of life
questionnaire, and mental functions tests will be repeated 12 weeks after the treatment. Some
blood tests, however, may be done by a local doctor. The test results would then be sent to
the study coordinator. The follow-up visits will end after 12 weeks.

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.