GBM, Glioblastoma Multiforme
Conditions
Keywords
FET, Fluoroethyl tyrosine, GBM, Response to treatment, Avastin, Brain Tumor
Brief 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.
Interventions
DRUG18F-FET
Radiotracer, surrogate marker for protein synthesis
Sponsors
Marcelo F. Di Carli, MD, FACC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From date of baseline PET scan until the date of death from any cause, assessed up to 2 years. | The primary objective is to assess the utility of FET-PET imaging for prediction of progression-free survival in recurrent glioblastoma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of baseline PET scan until the date of death from any cause, assessed up to 2 years. | The secondary objective is to assess the utility of FET-PET imaging for prediction of overall survival in recurrent glioblastoma. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GBM Avastin Receiving 18F-FET Recurrent GBM patients receiving Avastin, imaged twice with 18F-FET PET before and approximately 8 weeks after receiving Avastin
18F-FET: Radiotracer, surrogate marker for protein synthesis | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | moved away and lost to followup | 1 |
Baseline characteristics
| Characteristic | GBM Avastin Receiving 18F-FET |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 61.4 years |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 12 |
| other Total, other adverse events | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Progression-free Survival
The primary objective is to assess the utility of FET-PET imaging for prediction of progression-free survival in recurrent glioblastoma.
Time frame: From date of baseline PET scan until the date of death from any cause, assessed up to 2 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GBM Avastin Receiving 18F-FET | Progression-free Survival | 158.25 days | Standard Deviation 161.7 |
Secondary
Overall Survival
The secondary objective is to assess the utility of FET-PET imaging for prediction of overall survival in recurrent glioblastoma.
Time frame: From date of baseline PET scan until the date of death from any cause, assessed up to 2 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GBM Avastin Receiving 18F-FET | Overall Survival | 270.58 days | Standard Deviation 222 |