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

• Sponsor: Marcelo F. Di Carli, MD, FACC (Other)
• Overall Status: Completed
• CT.gov ID: NCT01756352
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 31.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme; GBM	Drug: 18F-FET	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Assessment of the Utility of the Radiotracer "FET"in PET Imaging of Recurrent Glioblastoma Multiforme (GBM): Monitoring Early Response to Antiangiogenic Therapy
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Sep 13, 2015
• Actual Study Completion Date: Sep 13, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Marcelo F. Di Carli, MD, FACC

Investigators

• Principal Investigator: Raymond L Huang, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marcelo F. Di Carli, MD, FACC, Chief of Nuclear Medicine/PET, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01756352
• Other Study ID Numbers: 2012P002678
• First Posted: Dec 25, 2012
• Last Update Posted: Oct 30, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Marcelo F. Di Carli, MD, FACC, Chief of Nuclear Medicine/PET, Brigham and Women's Hospital: FET; Fluoroethyl tyrosine; GBM; Response to treatment; Avastin; Brain Tumor
• Additional relevant MeSH terms: Glioblastoma

Study Results

Participant Flow

Arm/Group Title	GBM Avastin Receiving 18F-FET
Arm/Group Description	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
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	GBM Avastin Receiving 18F-FET
Arm/Group Description	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
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 75%
>=65 years	3 25%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61.4
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GBM Avastin Receiving 18F-FET
Arm/Group Description	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
Measure Participants	12
Mean (Standard Deviation) [days]	158.25 (161.7)

2. Secondary Outcome

Title	Overall Survival
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GBM Avastin Receiving 18F-FET
Arm/Group Description	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
Measure Participants	12
Mean (Standard Deviation) [days]	270.58 (222.00)

Adverse Events

Time Frame	From date of baseline PET scan until the date of death from any cause, assessed up to 2 years.
Arm/Group Title	GBM Avastin Receiving 18F-FET
Arm/Group Description	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
All Cause Mortality
	GBM Avastin Receiving 18F-FET
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Serious Adverse Events
	GBM Avastin Receiving 18F-FET
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	GBM Avastin Receiving 18F-FET
	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)
Vascular disorders
Bruising	2/12 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.