Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00430079
First received: January 30, 2007
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

This clinical trial is using EF5 to measure the oxygen level in tumor cells of patients undergoing surgery or surgery biopsy for newly diagnosed supratentorial malignant glioma. Diagnostic procedures using the drug EF5 to measure the oxygen level in tumor cells may help in planning cancer treatment


Condition Intervention
Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Anaplastic Oligodendroglioma
Adult Diffuse Astrocytoma
Adult Ependymoma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Adult Myxopapillary Ependymoma
Adult Oligodendroglioma
Adult Pilocytic Astrocytoma
Adult Pineal Gland Astrocytoma
Adult Subependymoma
Drug: etanidazole
Procedure: conventional surgery
Other: pharmacological study
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Assessment of Hypoxia in Malignant Gliomas Using EF5

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to local recurrence [ Time Frame: Time from study entry (EF5 administration) to local recurrence, assessed up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to death [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Presence and pattern of EF5 binding in newly diagnosed brain masses by IHC analyses [ Time Frame: At 48 hours after EF5 administration ] [ Designated as safety issue: No ]
  • Levels of EF5 binding within histological subtypes of SMG [ Time Frame: At baseline, at 1 hour, and the time of surgery ] [ Designated as safety issue: No ]
  • Relationship between hypoxia and clinical outcomes (i.e., time to local recurrence and survival) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Time to local recurrence and survival will be estimated by the method of Kaplan and Meier.

  • Association between EF5 binding and Eppendorf needle electrode measurements in brain masses [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The correlation between median oxygen pressure (pO2) by Eppendorf electrode measurement and percent of maximal signal in tumors (by EF5 binding) will be assessed by Pearson's correlation coefficient.


Enrollment: 48
Study Start Date: July 2001
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diagnostic (etanidazole)
Patients receive etanidazole derivative EF5 IV over 1-2½ hours once within 1-2 days before surgical resection or biopsy. Tumor tissue, normal tissue, and/or tumor-infiltrated lymph node samples are collected during surgery and stained for biological markers. Fluorescent immunohistochemistry techniques are used to determine the presence, distribution, and levels of EF5 binding.
Drug: etanidazole
Given IV
Other Names:
  • 2-nitro-imidazole derivative
  • SR-2508
Procedure: conventional surgery
Undergo surgery
Other Name: surgery, conventional
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the presence and pattern of etanidazole derivative EF5 binding with tumor, based on image and cellular analyses, in patients undergoing surgery or biopsy for newly diagnosed supratentorial malignant gliomas.

II. Determine the level of EF5 binding within histologic subtypes of this tumor in these patients.

Compare the relationship between hypoxia and clinical outcomes in patients with glioblastoma multiforme (GBM) vs non-GBM.

III. Determine the spatial relationships between EF5 binding and tumor tissue biomarkers and pathophysiologic processes (e.g., necrosis, proliferation, and apoptosis) in these patients.

IV. Determine the relationship between EF5 binding and Eppendorf needle electrode measurements in these patients.

OUTLINE:

Patients receive etanidazole derivative EF5 IV over 1-2½ hours once within 1-2 days before surgical resection or biopsy. Tumor tissue, normal tissue, and/or tumor-infiltrated lymph node samples are collected during surgery and stained for biological markers. Fluorescent immunohistochemistry techniques are used to determine the presence, distribution, and levels of EF5 binding.

Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1½-2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed and/or clinical and imaging evidence of a new brain mass that is likely to be a supratentorial malignant glioma
  • Clinical condition and physiologic status indicative of debulking surgery or biopsy as standard initial therapy
  • Performance status - Karnofsky performance status 60-100%
  • WBC greater than 2,000/mm^3
  • Platelet count greater than 90,000/mm^3
  • Creatinine less than 2.0 mg/dL
  • No significant cardiac condition that would preclude study therapy
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 month after study completion
  • Weight no greater than 130 kilograms
  • No grade 3 or 4 peripheral neuropathy
  • No other invasive malignancy within the past 3 years that is likely to cause a solitary supratentorial metastasis
  • No uncontrolled concurrent illness, medical condition, psychiatric illness, or social situation that would preclude study participation
  • At least 6 months since prior chemotherapy
  • Concurrent corticosteroid therapy allowed
  • At least 6 months since prior radiotherapy to lesion or site of lesion
  • At least 6 months since prior surgery to lesion or site of lesion except incisional or core biopsy
  • Concurrent anticonvulsant therapy allowed
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00430079

Locations
United States, Pennsylvania
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Principal Investigator: Kevin Judy Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00430079     History of Changes
Other Study ID Numbers: NCI-2012-02419, UPCC# 1301, R21CA093007, CDR0000068962
Study First Received: January 30, 2007
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Ependymoma
Glioblastoma
Glioma
Oligodendroglioma
Glioma, Subependymal
Gliosarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etanidazole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014