FET-PET for Evaluation of Response of Recurrent GBM to Avastin

Assessment of the Utility of the Radiotracer "FET"in PET Imaging of Recurrent Glioblastoma Multiforme (GBM): Monitoring Early Response to Antiangiogenic Therapy

Hypothesis: The central hypothesis underlying the proposed research study is that FET-PET will predict durable benefit in patients receiving anti-angiogenic benefit for presumed recurrent GBM (i.e. progression-free survival and overall survival). We have defined one primary specific aim, for which we expect to obtain definitive results, and two secondary aims, under which we plan to generate preliminary data to support a future, larger project.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme; GBM
• Intervention / Treatment: Drug: 18F-FET

Detailed Description

The PET radiotracer FET provides a measure of large, neutral amino acid transport. This transport is significantly upregulated in malignant brain tumors. FET rarely gives false positive findings in the setting of inflammation seen after high dose chemotherapy or radiotherapy. FET labels low-grade as well as high-grade gliomas, in contrast to FDG, which almost exclusively labels only high-grade gliomas. FET imaging may prove to be particularly useful in the setting of infiltrative tumor, which is not contrast-enhancing on MRI and therefore not detectable with FDG. Management of glioblastoma patients with stable contrast-enhancing disease on MRI but increased signs of edema is difficult. This is because it is difficult to distinguish simple edema from infiltrative tumor. The former is managed with steroids and the latter is managed with chemotherapy, and anti-angiogenic drugs.

FET may be particularly useful in assessing changes after GBM patients receive anti-vascular agents such as Avastin. Avastin is very commonly used in patients after failure of first-line treatment in GBM. Not only is Avastin costly, but it also can have serious side effects such as internal bleeding and gastric perforation, severe hypertension, poor wound healing, and renal toxicity. It is important to know when a patient is failing Avastin treatment so that the drug can be discontinued. Preliminary data in Europe (see figures below) suggests that FET-PET can accurately distinguish Avastin responders from non-responders.

Inclusion Criteria:

1. GBM patients with changes on MRI suggestive of recurrence who have not yet initiated antiangiogenic therapy.
2. Age ≥ 18
3. Anticipated survival >3 months
4. Able to give informed consent
5. Capable of undergoing scan without the need for sedation or general anesthesia.

Exclusion Criteria:

1. Active intracranial infection or nonglial brain mass.
2. Recent large intracranial hemorrhage (<1 month; size to be determined by principal investigator)
3. Pregnant or nursing. Quantitative serum hCG testing will be performed prior to the initial and each -subsequent FET- PET scan on all females of childbearing potential. Our BWH Radiation Safety Committee and Partners IRB requires stat serum ß-hcG pregnancy tests.
4. Patient lives too far from BWH and/or is unwilling/ unable to return for scheduled imaging visits.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. GBM patients with changes on MRI suggestive of recurrence who have not yet initiated antiangiogenic therapy. 2. Age ≥ 18 3. Anticipated survival >3 months 4. Able to give informed consent 5. Capable of undergoing scan without the need for sedation or general anesthesia.

Exclusion Criteria:

1. Active intracranial infection or nonglial brain mass.
2. Recent large intracranial hemorrhage (<1 month; size to be determined by principal investigator)
3. Pregnant or nursing. Quantitative serum hCG testing will be performed prior to the initial and each -subsequent FET- PET scan on all females of childbearing potential. Our BWH Radiation Safety Committee and Partners IRB requires stat serum ß-hcG pregnancy tests.

4. Patient lives too far from BWH and/or is unwilling/ unable to return for scheduled imaging visits.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GBM Avastin receiving 18F-FET; Recurrent GBM patients receiving Avastin, imaged twice with 18F-FET PET before and approximately 8 weeks after receiving Avastin	Drug: 18F-FET; Radiotracer, surrogate marker for protein synthesis; Other Names: 18F-Fluoroethyltyrosine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	The primary objective is to assess the utility of FET-PET imaging for prediction of progression-free survival in recurrent glioblastoma.	From date of baseline PET scan until the date of death from any cause, assessed up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The secondary objective is to assess the utility of FET-PET imaging for prediction of overall survival in recurrent glioblastoma.	From date of baseline PET scan until the date of death from any cause, assessed up to 2 years.

Collaborators and Investigators

• Sponsor: Marcelo F. Di Carli, MD, FACC
• Investigators: Principal Investigator: Raymond L Huang, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): September 13, 2015
• Study Completion (Actual): September 13, 2015

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: December 24, 2012
• First Posted (Estimate): December 25, 2012

Study Record Updates

• Last Update Posted (Actual): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 25, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Brain Tumor; GBM; Avastin; FET; Fluoroethyl tyrosine; Response to treatment
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 2012P002678