This study will evaluate the safety and efficacy of a chemotherapeutic drug (topotecan) as it is given directly into brain tumors by a delivery technique called convection-enhanced delivery. This drug has been used for different types of cancer, but in this study it will be given by an experimental delivery technique designed to maximize the amount of drug delivered to the brain tumor and minimize the side effects in other parts of the body.

This study will also evaluate advanced magnetic resonance (MR) imaging techniques.

The study will assess quality of life parameters throughout the follow-up period.

Clinical efficacy with chemotherapy has been discouraging for malignant brain tumors, mostly because of side effects and delivery limitations. Because they are locally invasive and rarely metastasize, malignant gliomas have features that make them uniquely amenable to new strategies of regional drug delivery. Intracerebral clysis (convection-enhanced delivery) is a novel drug delivery strategy that uses a microinfusion pump to establish a pressure gradient in the brain via implanted catheters. The pressure gradient produces convective forces that distribute a therapeutic agent throughout the tumor and surrounding brain tissue.

Non-invasive magnetic resonance imaging (MRI) methods of monitoring drug distribution and treatment response have been developed to maximize the clinical applications and minimize complications associated with treatment risks.

Study participants will be taken to the operating room to have 2 catheters surgically placed into their tumor and surrounding tumor bed. These catheters will then be connected to small infusion pumps which will slowly infuse topotecan continuously over 4-5 days. Patients will have daily MRI scans while in the hospital. Upon completion of the experimental treatment, patients will be discharged and will be followed up in the outpatient clinic.

Inclusion Criteria:

• Patients with primary malignant brain tumor, or a newly diagnosed or recurrent malignant tumor of the brainstem. Patients with tumors of the brain must have been previously treated with external beam radiation. Patients with brainstem gliomas may or may not have been previously treated.
• Patients with a tumor that is stereotactically accessible (MR scan must be obtained within 30 days of enrollment and must demonstrate an enhancing mass without significant mass effect. Tumors must be less than 100 cc in total volume).
• Patients who demonstrate evidence of increasing contrast enhancement on MR or CT imaging while on stable or increasing dose of steroid.
• Patients with a Karnofsky Performance Score of greater than or equal to 60.
• Men and women of child-bearing potential must practice birth control. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of study entry.
• Patients must possess the ability to give Informed Consent. Parent or guardian may give informed consent for minors.
• Patients must be willing to and medically capable of undergoing the surgical operation.
• Patients may not be receiving other investigational agents for the treatment of malignant astrocytoma.
• There is no upper age limit. Patients at extreme upper end of the age spectrum will not be automatically excluded, but will be carefully scrutinized to determine their suitability for this procedure.
• Patients must be at least 1 year old to participate in the study.

Exclusion Criteria:

• Patients with diffuse subependymal or cerebrospinal fluid (CSF) disease.
• Patients with tumors involving the cerebellum, or both hemispheres.
• Patients with an active infection requiring treatment or having an unexplained febrile illness.
• Patients who are known HIV positive or who are known positive for Hepatitis B or C virus
• Patients who have received any form of radiation or chemotherapy within 4 weeks of protocol enrollment.
• Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.
• Patients who have previously received systemic topotecan for their tumor
• Patients less than 1 year of age
• Patients who are not able to receive an MRI scan