A Pilot Feasibility, Dose-Escalation Study Using Intracerebral Microdialysis to Assess the Neuropharmacodynamics of Temsirolimus in Patients With Primary or Metastatic Brain Tumors
- Determine the feasibility of using a microdialysis catheter with a high cut-off
membrane to perform neuropharmacodynamics (nPD) assessment of targeted therapy with a
mammalian target of rapamycin (mTOR) inhibitor, where nPD is defined as changes in
intracerebral levels of vascular endothelial growth factor (VEGF), interleukin-1ß
(IL-1ß), and other cytokines.
- Assess the relationship between temsirolimus dose and changes in intracerebral levels
of VEGF, IL-1ß, and other cytokines.
- Compare changes in intracerebral cytokine levels to changes in systemic cytokine
- Assess the relationship between the degree of microvascular proliferation and the
tensin homologue deleted on chromosome 10 (PTEN) status in tumor tissue.
- Assess the relationship between changes in intracerebral cytokine levels after
treatment with temsirolimus.
OUTLINE: Two cohorts of 6 patients will be enrolled in this study. All patients undergo
debulking craniotomy or stereotactic biopsy and a placement of a intracerebral CMA 71
microdialysis (ICMD) catheter. Patients then are assigned to 1 of 2 treatment cohorts.
- Cohort 1: Patients do not receive temsirolimus. Dialysate samples will be collected at
regular intervals during the 96 hours following placement of the catheter as well as
serial blood samples to measure levels of cytokines, chemokines and growth factors that
occur after neurosurgery.
- Cohort 2: Beginning 48 hours after surgery, patients receive a single 200 mg dose of
temsirolimus IV. Dialysate samples will be collected at regular intervals during the 96
hours following placement of the catheter as well as serial blood samples to measure
levels of cytokines, chemokines and growth factors that occur after neurosurgery.
Plasma levels of temsirolimus and sirolimus will also be measured from the serial blood
After completion of study therapy and removal of ICMD catheter, patients are followed for 30
Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of using a microdialysis catheter to assess the neuropharmacodynamics (nPD) of temsirolimus
Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately
Jana Portnow, MD
Beckman Research Institute
United States: Food and Drug Administration
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|