FET-PET for Evaluation of Response of Recurrent GBM to Avastin
Condition: Glioblastoma Multiforme; GBM
MeSH terms: Glioblastoma
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): 18F-FET
Intervention type(s): Drug
Intervention description(s): Radiotracer, surrogate marker for protein synthesis
Other intervention name(s): 18F-Fluoroethyltyrosine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: FET; Fluoroethyl tyrosine; GBM; Response to treatment; Avastin; Brain Tumor