Pharmacologic Study of Methotrexate in Patients Undergoing Stereotactic Biopsy for Recurrent High-Grade Glioma

• ClinicalTrials.gov Identifier: NCT00463008
• Recruitment Status: Completed
• First Posted: April 19, 2007
• Last Update Posted: June 24, 2013
• Sponsor: New Approaches to Brain Tumor Therapy Consortium
• Collaborator: National Cancer Institute (NCI)
• Information provided by: National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: methotrexate; Other: pharmacological study	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Non-Randomized
• Primary Purpose: Treatment
• Official Title: A Pharmacokinetic Study of Methotrexate Using an Intratumoral Microdialysis Catheter
• Study Start Date: May 2004
• Actual Study Completion Date: April 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Comparison of methotrexate levels in the brain extracelluar fluid vs in the serum
2. Safety and efficacy of the microdialysis catheter

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Sponsors and Collaborators

New Approaches to Brain Tumor Therapy Consortium

National Cancer Institute (NCI)

Investigators

• Study Chair: Jeffrey J. Olson, MD; Emory University
• OverallOfficial: Stuart A. Grossman, MD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

More Information

• ClinicalTrials.gov Identifier: NCT00463008
• Other Study ID Numbers: CDR0000346432; NABTT-0302; JHOC-NABTT-0302
• First Posted: April 19, 2007
• Last Update Posted: June 24, 2013
• Last Verified: January 2008

Keywords provided by National Cancer Institute (NCI):

adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult glioblastoma; recurrent adult brain tumor; adult gliosarcoma; adult giant cell glioblastoma

Additional relevant MeSH terms:

Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors