A Pilot 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
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.
OBJECTIVES:
Primary
Secondary
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.
After completion of study therapy and removal of ICMD catheter, patients are followed for 30 days.
Inclusion Criteria
Patients must be at least 18 years of age.
Patients must have either a primary or metastatic brain tumor(s).
Patients must be in need of a surgical debulking or a stereotactic biopsy for the purpose of diagnosis or differentiating between tumor progression and treatment-induced effects following radiation therapy + or - chemotherapy.
For patients in cohort 2, treatment with temsirolimus must not be contraindicated.
Patients in cohort 2 must not be taking any hepatic enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine).
Patients who are taking strong CYP3A4 inducers or inhibitors such as clarithromycin, itraconazole, ketoconazole, nefazodone, telithromycin, rifampin, rifabutin, rifampacin, or St. John's Wort must discontinue the medication beginning at least one week prior to surgery and lasting for the duration of the study. The only exception will be dexamethasone which can be used post-operatively as indicated.
Patients must have a Karnofsky Performance Status >= 60% or an ECOG/Zubrod score of<= 2.
Patients must have recovered from any toxicity of any prior therapy.
Patients must have adequate bone marrow function (defined as an absolute neutrophil count of >= 1500 cells/mm3 and platelet count ≥ 100,000 cells/mm3), liver function with total bilirubin <= 2.0 mg/dl and AST (SGOT) <= 4 times the institutional upper limit of normal, and serum creatinine <=1.5 x the institutional upper limit of normal.
Patients must be able to understand and be willing to sign a written informed consent document.
The effects of temsirolimus on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients must agree to use an effective method of contraception while participating in this study. Women of childbearing potential must have a negative pregnancy test <=2 weeks prior to registration.
Exclusion Criteria
Patients must not be planning to receive radiation, other chemotherapy or participate in another clinical trial from the time of surgery until the microdialysis catheters is removed.
Patients allergic to temsirolimus, sirolimus (rapamycin), or Dextran.
Patients with a coagulopathy, increased susceptibility to infection or bleeding disorders.
Patients on anticoagulant drug therapy.
Patients with uncontrolled diabetes.
Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Female patients who are pregnant or breast-feeding.
HIV-positive patients receiving anti-retroviral therapy are excluded from the study due to the possibility of PK interactions with temsirolimus; however, patients will not be routinely screened for HIV.