Official Title: “A Pharmacokinetic Study of Methotrexate Using an Intratumoral Microdialysis Catheter”

RATIONALE: Collecting fluid from a brain tumor using a small catheter may help doctors learn how much methotrexate gets into the tumor to kill the tumor cells. It may also help doctors learn how methotrexate works in the brain and in the rest of the body.

PURPOSE: This clinical trial is studying how much methotrexate gets into the brain tumor by collecting fluid directly from the tumor through a small catheter in patients undergoing stereotactic biopsy for recurrent high-grade glioma.

Study Type: Interventional

Study Design: Treatment, Non-Randomized

OBJECTIVES: - Determine the feasibility of using microdialysis to study distribution of systemically administered methotrexate in the interstitial fluid within a tumor in patients undergoing stereotactic biopsy for recurrent high-grade gliomas. - Determine the systemic and intratumoral pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients have an intratumoral microdialysis catheter placed while undergoing stereotactic biopsy. Between 18-32 hours after placement of catheter, patients receive methotrexate IV over 4 hours. Microdialysis perfusate and blood specimens are collected before, during, and for 24 hours after methotrexate administration.

Patients are followed at 2 weeks.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 6 months.

Intervention(s) in this Clinical Trial

• Drug: methotrexate
• Procedure: pharmacological study

Primary Measures

• Comparison of methotrexate levels in the brain extracelluar fluid vs in the serum
  • Safety Issue?: No
• Safety and efficacy of the microdialysis catheter
  • Safety Issue?: Yes

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade III or IV astrocytoma of 1 of the following subtypes:
• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Glioblastoma multiforme
• Measurable, contrast-enhancing, residual disease by MRI or CT scan
• Undergoing stereotactic biopsy for confirmation of tumor progression or differentiation of tumor progression from treatment-induced effects
• Patients with prior low-grade glioma that progressed after prior radiotherapy with or without chemotherapy and in need of stereotactic biopsy to confirm high-grade glioma are eligible
• Must have received prior radiotherapy with or without chemotherapy
• Planning to continue methotrexate therapy after participation on this study
• No ascites or pleural effusions

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 2.0 mg/dL
• SGOT ≤ 4 times upper limit of normal
• Creatinine ≤ 2 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ
• Able to achieve hydration necessary for the use of methotrexate
• Mini mental state exam score at least 15
• No allergy to methotrexate
• No other concurrent infection or medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 3 months since prior radiotherapy
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• At least 1 week since prior salicylates, nonsteroidal anti-inflammatory drugs, or sulfonamides
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent chemotherapeutic agents
• No other concurrent investigational agents

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

Jeffrey J. Olson, MD Study Chair Emory University  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00463008

Study ID Number: CDR0000346432

ClinicalTrials.gov Identifier: NCT00463008

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database