Clinical trial NCT00463008: Pharmacologic Study of Methotrexate in Patients Undergoing Stereotactic Biopsy for Recurrent High-Grade Glioma
Official title: A Pharmacokinetic Study of Methotrexate Using an Intratumoral Microdialysis Catheter
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain and Central Nervous System Tumors
Keywords: adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult glioblastoma
recurrent adult brain tumor
adult gliosarcoma
adult giant cell glioblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of methotrexate levels in the brain extracelluar fluid vs in the serum
measure: Safety and efficacy of the microdialysis catheter
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Emory University
name: Jeffrey J. Olson, MD
role: STUDY_CHAIR
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Stuart A. Grossman, MD
References: