NCT00784914

A Feasibility, Dose-Escalation Study Using Intracerebral Microdialysis to Assess the Neuropharmacodynamics of Temsirolimus in Patients With Primary or Metastatic Brain Tumors

A Pilot Feasibility, Dose-Escalation Study Using Intracerebral Microdialysis to Assess the Neuropharmacodynamics of Temsirolimus in Patients With Primary or Metastatic Brain Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Studying samples of blood and tumor tissue from patients with cancer in the laboratory may help doctors learn more about how this treatment is used by the body. PURPOSE: The purpose of this study is to evaluate the feasibility of using a microdialysis catheter to see what effect temsirolimus has on various biological substances associated with brain tumors over time.

Detailed description

OBJECTIVES: Primary * 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. Secondary * 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 levels. * 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 samples. After completion of study therapy and removal of ICMD catheter, patients are followed for 30 days.

Conditions

• Brain and Central Nervous System Tumors
• Metastatic Cancer

Interventions

Type	Name	Description
DRUG	temsirolimus	Receive temsirolimus IV
OTHER	pharmacological study	Plasma levels of temsirolimus and sirolimus will be evaluated in serial blood samples.
OTHER	cytokine levels	Dialysate samples are collected at regular intervals during the 96 hours following placement of the catheter to measure changes in levels of cytokines, chemokines and growth factors

Timeline

• Start date: 2008-06-01
• Primary completion: 2010-11-01
• Completion: 2010-11-01
• First posted: 2008-11-04
• Last updated: 2018-04-17

Locations

1 site across 1 country: United States