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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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.
  • Sponsor: City of Hope Medical Center

    Current Primary Outcome:

    • Feasibility of using a microdialysis catheter to assess the neuropharmacodynamics (nPD) of temsirolimus [ Time Frame: Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately ]
    • Changes in intracerebral levels of vascular endothelial growth factor (VEGF), interleukin-1ß (IL-1ß), and other cytokines [ Time Frame: Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately ]


    Original Primary Outcome:

    • Feasibility of using a microdialysis catheter to assess the neuropharmacodynamics (nPD) of temsirolimus with and without temozolomide
    • Changes in intracerebral levels of VEGF, IL-1ß, and other cytokines


    Current Secondary Outcome:

    • Relationship between temsirolimus dose and changes in intracerebral levels of VEGF, IL-1ß, and other cytokines [ Time Frame: Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately ]
    • Relationship between the degree of microvascular proliferation and the tensin homologue deleted on chromosome 10 (PTEN) status in tumor tissue [ Time Frame: 30 days after placement of the microdialysis catheter. ]
    • Relationship between changes in intracerebral cytokine levels after treatment with temsirolimus [ Time Frame: Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately ]
    • Compare changes in intracerebral cytokine levels to changes in systemic cytokine levels. [ Time Frame: Every 6 hours for 96 hours after confirmation that the microdialysis catheter is placed appropriately ]


    Original Secondary Outcome:

    • Relationship between temsirolimus dose and changes in intracerebral levels of VEGF, IL-1ß, and other cytokines
    • Affect of temozolomide on the nPD of temsirolimus when the two agents are given concurrently versus temsirolimus alone
    • Relationship between the degree of microvascular proliferation and the tensin homologue deleted on chromosome 10 (PTEN) status in tumor tissue
    • Relationship between changes in intracerebral cytokine levels after treatment with temsirolimus


    Information By: City of Hope Medical Center

    Dates:
    Date Received: November 1, 2008
    Date Started: June 2008
    Date Completion:
    Last Updated: September 24, 2015
    Last Verified: September 2015