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

Adult Glioblastoma Clinical Trial

Official title:

Assessment of Hypoxia in Malignant Gliomas Using EF5

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00430079
• Other study ID #: NCI-2012-02419
• Secondary ID: UPCC# 1301R21CA0
• Status: Terminated
• Phase: N/A
• First received: January 30, 2007
• Last updated: January 15, 2013
• Start date: July 2001

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• 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
• Astrocytoma
• Ependymoma
• Glioblastoma
• Glioma
• Gliosarcoma
• Oligodendroglioma

Intervention

Drug:
• etanidazole
Given IV

Procedure:
• conventional surgery
Undergo surgery

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to local recurrence		Time from study entry (EF5 administration) to local recurrence, assessed up to 3 years	No
Secondary	Time to death		Up to 3 years	No
Secondary	Presence and pattern of EF5 binding in newly diagnosed brain masses by IHC analyses		At 48 hours after EF5 administration	No
Secondary	Levels of EF5 binding within histological subtypes of SMG		At baseline, at 1 hour, and the time of surgery	No
Secondary	Relationship between hypoxia and clinical outcomes (i.e., time to local recurrence and survival)	Time to local recurrence and survival will be estimated by the method of Kaplan and Meier.	Up to 3 years	No
Secondary	Association between EF5 binding and Eppendorf needle electrode measurements in brain masses	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.	Up to 3 years	No