Trial Information

A Pilot Feasibility Study of Intracerebral Microdialysis to Determine the Neuropharmacokinetics of Temozolomide

OBJECTIVES:

- Determine the feasibility of microdialysis for assessing the intracerebral distribution
of temozolomide in patients with primary or metastatic brain tumors.

- Determine the interstitial pharmacokinetics of temozolomide using an intracerebral
microdialysis catheter in these patients.

- Determine the feasibility of assessing brain tumor metabolism using a microdialysis
catheter to measure intracerebral levels of glucose, lactate, pyruvate, glutamate, and
glycerol in these patients.

OUTLINE: Patients are assessed for viable tumor during a debulking craniotomy or
stereotactic biopsy. If viable tumor is confirmed, patients undergo placement of an
intracerebral microdialysis (MD) catheter. The catheter, which is perfused continuously over
24 hours with artificial cerebrospinal fluid, is placed directly into the residual brain
tumor or peritumoral brain tissue for neuropharmacokinetic studies of temozolomide. At least
25 hours but no more than 72 hours after placement of the catheter, patients receive a
single dose of oral temozolomide. At the same time, intracerebral MD is initiated and serial
samples of dialysate (i.e., brain extracellular fluid [ECF]) are collected periodically over
24 hours for analysis of intracerebral concentrations of temozolomide by liquid
chromatography/tandem mass spectrometry. Serial blood samples for measuring plasma levels of
temozolomide are also drawn and plasma temozolomide levels are compared with those in the
brain ECF. Additional ECF samples are obtained to assess biochemical markers of brain tumor
metabolism (i.e., glucose, lactate, pyruvate, glutamate, or glycerol) at least one hour
before and 24 hours after administration of temozolomide.

After completion of study therapy, patients are followed for up to 30 days.