Temozolomide in Treating Patients With Primary Brain Tumors or Metastatic Brain Tumors

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00547131
• Other study ID #: 05117
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 1
• First received: October 19, 2007
• Last updated: April 12, 2018
• Start date: January 2006
• Est. completion date: May 2009

Study information

• Verified date: April 2018
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Collecting fluid samples through a catheter may help doctors find out how well temozolomide spreads throughout the brain.

PURPOSE: This clinical trial is studying temozolomide in treating patients with primary brain tumors or metastatic brain tumors.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of a primary or metastatic brain tumor for which temozolomide would be an appropriate chemotherapy treatment postoperatively

• Disease requires a debulking craniotomy or a stereotactic biopsy to diagnose or differentiate between tumor progression and treatment-induced effects after radiotherapy with or without chemotherapy

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• ANC = 1,500/mm³

• Platelet count = 100,000/mm³

• Total bilirubin = 2.0 mg/dL

• AST = 4 times upper limit of normal (ULN)

• Creatinine = 1.5 time ULN

• Mini Mental Status Exam score = 15

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No allergy to temozolomide

• No serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• No concurrent chemotherapy or radiotherapy during the period of time that the microdialysis catheter is placed intracerebrally and until it is removed

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis
• Nervous System Neoplasms

Intervention

Drug:
• temozolomide

Other:
• laboratory biomarker analysis

• liquid chromatography

• mass spectrometry

• pharmacological study

Procedure:
• conventional surgery

Radiation:
• stereotactic radiosurgery

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	City of Hope Medical Group	Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of clinically symptomatic intratumoral hemorrhage
Primary	Incidence rate of CNS infection
Primary	Incidence rate of catheter malfunction
Secondary	Systemic and intracerebral pharmacokinetic profile of temozolomide using a microdialysis catheter