Chronic Convection Enhanced Delivery of Topotecan

• Status: Active, not recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary goal of this study is to establish, for the first time, safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients with recurrent high grade glioma (HGG). Secondary objectives will include determination of topotecan (TPT) distribution and radiographic tumor response with prolonged continuous intracerebral convection-enhanced delivery (CED).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jeffrey N. Bruce
• Collaborator: National Cancer Institute (NCI)
• Treatments: Topotecan

Criteria

Inclusion Criteria:

• Patients must have a recurrent malignant glioma (World Health Organization (WHO) grade III-IV), including recurrent glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma. Stereotactic biopsies will be performed to confirm this diagnosis prior to initiating the treatment.

• Patients with tumors of the brain must have been previously treated with surgical resection, external beam radiation, and temozolomide chemotherapy.

• An magnetic resonance (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 32 cc in total volume. The lesion must be stereotactically accessible.

• Patients must have demonstrated evidence of increasing contrast enhancement on MR or computed tomography (CT) imaging while on stable or increasing dose of steroid.

• Karnofsky performance score of greater than or equal to 60.

• Men and women of childbearing potential must practice birth control. Women of child bearing potential must have a urine pregnancy test within 7 days of study entry.

• Patients must possess the ability to give Informed Consent.

• Patients must be willing to and medically capable of undergoing the surgical operation.

• 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 18 years old.

• Patients must have normal organ and marrow function as defined below:

• Leukocytes: ≥3,000/ cells per microliter of blood (mcL)

• Absolute neutrophil count: ≥1,500/mcL

• Platelets: ≥100,000/mcL

• Total bilirubin: within normal institutional limits

• aspartate aminotransferase (AST) (SGOT)/alanine aminotransferase (ALT) (SGPT):

≤2.5 × institutional upper limit of normal

• Creatinine: within normal institutional limits OR

• Creatinine clearance: ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Exclusion Criteria:

• Patients with diffuse subependymal or cerebral spinal fluid (CSF) disease.

• Patients with tumors involving the cerebellum or both cerebral hemispheres.

• Patients with an active infection requiring treatment or having an unexplained febrile illness.

• Patients who are known HIV, Hepatitis B or Hepatitis C positive. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with topotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

• Patients with systemic diseases which may be associated with unacceptable anesthetic/operative risk.

• Patients who have previously received systemic topotecan for their tumor

• Patients who are not able to receive an MRI scan.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, other topoisomerase inhibitors or gadolinium compounds.