Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

Phase 1

Terminated

• Conditions: Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma
• Interventions: Procedure: conventional surgery; Drug: EF5; Procedure: positron emission tomography; Radiation: fluorine F 18 EF5; Other: pharmacological study

• Registration Number: NCT00110032
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase I trial is studying the side effects of fluorine F18 EF5 when given during positron emission tomography to find oxygen in tumor cells of patients who are undergoing surgery or biopsy for newly diagnosed brain tumors. Diagnostic procedures using fluorine F 18 EF5 and positron emission tomography to detect tumor hypoxia may help in planning cancer treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety of fluorine F 18 EF5 (\^18F-EF5) in patients with newly diagnosed brain tumors undergoing surgery or biopsy.

Secondary I. Determine the pharmacokinetics and biodistribution of \^18F-EF5 administered before and after nonradioactive EF5 in these patients.

II. Determine the ability of positron emission tomography (PET) scanning using \^18F-EF5 to detect tumor hypoxia in these patients.

III. Determine the presence and pattern of nonradioactive EF5 binding by immunohistochemistry (IHC) and/or flow cytometry in these patients.

IV. Correlate tumor hypoxia, as measured by PET scanning using \^18F-EF5, with EF5 staining by IHC and/or flow cytometry and recurrence-free survival of these patients.

OUTLINE: Patients are assigned to 1 of 3 groups.

Group 1: Patients receive fluorine F 18 EF5 (\^18F-EF5) IV followed by whole brain and whole body positron emission tomography (PET) scanning OR whole body PET scanning only. Patients then receive nonradioactive EF5 IV over 1-2 ½ hours.

Group 2: Patients receive nonradioactive EF5 IV over 1-2½ hours followed by \^18F-EF5 IV. Patients then undergo whole brain and whole body PET scanning.

Group 3: Patients receive nonradioactive EF5 and \^18F-EF5 as in group 2. Patients then undergo whole brain PET scanning. Approximately one day after EF5 administration, all patients undergo surgery or biopsy of the tumor AND biopsy of normal skin adjacent to the incision.

Patients are followed at 2-4 weeks and 4-6 weeks after EF5 administration and then every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Study Timeline

• Study First Submitted: 2005-05-03
• Study First Submitted QC: 2005-05-03
• Study First Posted: 2005-05-04
• Study Start: 2005-06
• Primary Completion: 2007-01
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-15
• Last Update Posted: 2013-01-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Histologically confirmed and/or clinical and imaging evidence of a de novo mass that is likely to be a brain tumor
• Amenable to debulking surgery or surgical resection or biopsy as standard initial therapy for the tumor
• Performance status - Karnofsky 70-100%
• At least 3 months
• WBC count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin < 1.2 mg/dL
• Creatinine < 1.3 mg/dL
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No other significant cardiac condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study participation
• Weight ≤ 130 kg
• No peripheral neuropathy ≥ grade 3
• No history of allergic reaction attributed to metronidazole
• No other uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance
• No other medical condition that would preclude study participation

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 (fluorine F 18 EF5, PET)	conventional surgery	Patients receive fluorine F 18 EF5 (\^18F-EF5) IV followed by whole brain and whole body PET scanning OR whole body PET scanning only. Patients then receive nonradioactive EF5 IV over 1-2 ½ hours.
Group 1 (fluorine F 18 EF5, PET)	positron emission tomography	Patients receive fluorine F 18 EF5 (\^18F-EF5) IV followed by whole brain and whole body PET scanning OR whole body PET scanning only. Patients then receive nonradioactive EF5 IV over 1-2 ½ hours.
Group 1 (fluorine F 18 EF5, PET)	fluorine F 18 EF5	Patients receive fluorine F 18 EF5 (\^18F-EF5) IV followed by whole brain and whole body PET scanning OR whole body PET scanning only. Patients then receive nonradioactive EF5 IV over 1-2 ½ hours.
Group 1 (fluorine F 18 EF5, PET)	pharmacological study	Patients receive fluorine F 18 EF5 (\^18F-EF5) IV followed by whole brain and whole body PET scanning OR whole body PET scanning only. Patients then receive nonradioactive EF5 IV over 1-2 ½ hours.
Group 3 (EF5, PET)	EF5	Patients receive nonradioactive EF5 and \^18F-EF5 as in group 2. Patients then undergo whole brain PET scanning.
Group 2 (EF5, PET)	EF5	Patients receive nonradioactive EF5 IV over 1-2½ hours followed by \^18F-EF5 IV. Patients then undergo whole brain and whole body PET scanning.
Group 2 (EF5, PET)	conventional surgery	Patients receive nonradioactive EF5 IV over 1-2½ hours followed by \^18F-EF5 IV. Patients then undergo whole brain and whole body PET scanning.
Group 2 (EF5, PET)	positron emission tomography	Patients receive nonradioactive EF5 IV over 1-2½ hours followed by \^18F-EF5 IV. Patients then undergo whole brain and whole body PET scanning.
Group 2 (EF5, PET)	pharmacological study	Patients receive nonradioactive EF5 IV over 1-2½ hours followed by \^18F-EF5 IV. Patients then undergo whole brain and whole body PET scanning.
Group 3 (EF5, PET)	conventional surgery	Patients receive nonradioactive EF5 and \^18F-EF5 as in group 2. Patients then undergo whole brain PET scanning.
Group 3 (EF5, PET)	positron emission tomography	Patients receive nonradioactive EF5 and \^18F-EF5 as in group 2. Patients then undergo whole brain PET scanning.
Group 3 (EF5, PET)	fluorine F 18 EF5	Patients receive nonradioactive EF5 and \^18F-EF5 as in group 2. Patients then undergo whole brain PET scanning.
Group 3 (EF5, PET)	pharmacological study	Patients receive nonradioactive EF5 and \^18F-EF5 as in group 2. Patients then undergo whole brain PET scanning.

Primary Outcome Measures

Name	Time	Method
Safety of F-18-EF5 based on the NCI CTCAE version 3.0	Up to 3 years	Summarized in descriptive statistics.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of radioactively labeled [F-18]-EF5	Day 1
Extent of hypoxia, determined by [F-18]-EF5 PET imaging	Up to day 1
IHC analysis of cold EF5	Up to day 1
Progression-free survival	Up to 6 years

Trial Locations

Locations (1)

Abramson Cancer Center of The University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States