Trial Title:
FET-PET-Guided Management of Pseudoprogression in Glioblastoma
NCT ID:
NCT06480721
Condition:
Glioblastoma
Radionecrosis of Brain
Conditions: Official terms:
Glioblastoma
Conditions: Keywords:
Glioblastoma
[¹⁸F] FET PET
Tumor progression
Pseudoprogression
Unnecessary interventions
Health-related quality of life
Healthcare costs
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Participants will be randomised in equal proportions between two arms: the
investigational arm and the control arm.
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan
Description:
Patients in the investigational arm will undergo the extra FET-PET scan, with use of the
O-(2-
¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) tracer. FET-PET scanning will be performed
according to the joint European Association of Nuclear Medicine (EANM)/European
Association of Neuro-Oncology (EANO)/Response Assessment in Neuro-oncology (RANO)
guidelines. In most patients, a static scan (20-40 minutes post-injection) will
performed. If the logistics of the research site allow for a dynamic scan (0-60 minutes
post-injection), this will be performed. Interpretation will be done by an experienced
nuclear medicine physician from the local center according to current European
guidelines. Central review will be performed by a panel of nuclear medicine physicians
from the study team. Clinical management is based on the index MRI and this additional
[¹⁸F] FET PET scan.
Arm group label:
Clinical management is based on the index MRI and an additional [¹⁸F] FET-PET together
Summary:
The goal of this diagnostic randomised clinical trial is to determine, in glioblastoma
patients with diagnostic uncertainty between pseudoprogression and tumor progression on
follow-up MRI after chemoradiation, the added value of a direct [¹⁸F] FET-PET scan for
clinical management.
The main questions it aims to answer are:
- Does the clinical management guided by an additional FET-PET scan leads to fewer
unnecessary interventions, compared with management based on MRI only?
- Does the clinical management guided by an additional FET-PET scan leads to better
health-related quality of life after 12 weeks, compared with management based on MRI
only?
- Does the clinical management guided by an additional FET-PET scan leads to reduced
net healthcare costs, compared with management based on MRI only?
Researchers will compare the investigational arm, where clinical management is based on
the index MRI scan and an additional FET-PET scan, with the control arm, where clinical
management is based solely on the index MRI scan, to investigate the added value of the
FET PET scan for clinical management.
Participants in the investigational arm will undergo the FET PET scan. All participants
will complete health-related quality of life questionnaires at four different timepoints.
Detailed description:
During follow-up of glioblastoma patients after chemoradiation, expert teams often
observe MRI abnormalities with difficulty in distinguishing between tumor growth and
pseudoprogression. Although techniques such as perfusion MRI provide additional
information, diagnostic uncertainty often remains, leading to incorrect or delayed
diagnosis and, inappropriate treatment, such as unnecessary surgery. Despite the good
discriminating power of [¹⁸F] Fluoro-ethyl-tyrosine-PET (FET-PET), this diagnostic tool
is not used frequently in the Netherlands due to costs, logistics, and misconceptions
about clinical benefit. In the FET POPPING study we aim to determine the added value of
[¹⁸F] FET-PET for clinical management. A multicenter diagnostic randomised clinical trial
will be performed, from July 2024 until December 2027. 144 adult patients with isocitrate
dehydrogenase (IDH)-wildtype glioblastoma will be included, who, after the concomitant
phase of chemoradiation, have increased contrast enhancement on MRI, causing doubt
between tumor growth or pseudoprogression. Included patients will be randomised 1:1 in
two arms. The investigational arm receives an additional [¹⁸F] FET-PET scan, and clinical
management is based on the index MRI and [¹⁸F] FET-PET together. Clinical management of
the control arm is based on the index MRI alone. Exact clinical management, following
from the available imaging, is chosen at the discretion of a multidisciplinary board. The
primary study endpoints are (a) the percentage of patients undergoing unnecessary
interventions and (b) health-related quality of life after 12 weeks. Secondary endpoints
include time-to-diagnosis, overall survival and cost-effectiveness. We hypothesize that
the clinical management guided by an additional [¹⁸F] FET-PET scan leads to fewer
unnecessary interventions, better health-related quality of life after 12 weeks and among
others reduced net healthcare costs, compared with management based on MRI only.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with a glioblastoma, IDH-wildtype, World Health Organization (WHO) grade 4,
according to WHO 2021 criteria.
- Age ≥18 years
- New or increased enhancement within the high-dose radiation field (defined as within
the 80% isodose line) on follow-up MRI
- Follow up MRI ≥3 months after the end of the standard-of-care temozolomide-based
concomitant chemoradiation (60 Gy/30 fractions or 40 Gy/15 fractions). Of note, very
early increase - within 3 months of last radiation - will not be grounds for
inclusion because of the high rate of pseudoprogression and slightly lower
diagnostic performance of FET-PET compared to the situation of increase beyond 3
months after last radiation. Patients with such very early increase may have
subsequent further increase after 3 months post-radiation, causing (further)
diagnostic doubt; these may be included at that later timepoint if they meet the
other inclusion criteria.
- First moment of clinicoradiological uncertainty regarding the diagnosis (≥3 months
after the end of chemoradiation): pseudoprogression or tumor recurrence. The
determination of 'uncertainty' is made by the treating physician, preferably in the
multidisciplinary tumor board, based on available clinical and standard-of-care
MRI-data, which generally includes perfusion-MRI.
- Previous usage of bevacizumab as a symptom treatment is allowed. However, inclusion
is only allowed at the first moment of clinical doubt between pseudoprogression and
tumor recurrence, not at later timepoints.
Exclusion Criteria:
- Previous treatment for recurrence of disease
- An enhanced lesion size of less than 1 cm on the index MRI. In the newest RANO PET
criteria, it is advised to use FET-PET for increasing lesions only in cases with a
minimum lesion size.
- Life expectancy of less than 6 months, determined by the treating physician
- Contra-indications for PET (claustrophobia, inability to lay still)
- Women of childbearing potential without adequate contraception
- Any other concomitant disease that may influence PET imaging or clinical outcomes of
this study, this includes but is not limited to: cerebral inflammatory diseases and
other cancers with brain- or leptomeningeal metastases
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Amsterdam UMC
Address:
City:
Amsterdam
Country:
Netherlands
Contact:
Last name:
Elsmarieke M van de Giessen, MD, PhD
Email:
E.m.vandegiessen@amsterdamumc.nl
Investigator:
Last name:
Elsmarieke M van de Giessen, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Haaglanden MC
Address:
City:
Den Haag
Country:
Netherlands
Contact:
Last name:
Maaike J Vos, MD, PhD
Email:
M.vos@haaglandenmc.nl
Investigator:
Last name:
Maaike J Vos, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Medisch Spectrum Twente
Address:
City:
Enschede
Country:
Netherlands
Facility:
Name:
UMC Groningen
Address:
City:
Groningen
Country:
Netherlands
Facility:
Name:
Maastricht UMC
Address:
City:
Maastricht
Country:
Netherlands
Facility:
Name:
Radboud UMC
Address:
City:
Nijmegen
Country:
Netherlands
Contact:
Last name:
Dylan JH Henssen, MD, PhD
Email:
Dylan.Henssen@radboudumc.nl
Investigator:
Last name:
Dylan JH Henssen, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Anne I Arens, MD, PhD
Email:
Sub-Investigator
Facility:
Name:
Erasmus MC
Address:
City:
Rotterdam
Country:
Netherlands
Contact:
Last name:
Sophie EM Veldhuijzen van Zanten, MD, PhD
Email:
s.veldhuijzenvanzanten@erasmusmc.nl
Investigator:
Last name:
Sophie EM Veldhuijzen van Zanten, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Marjolein Geurts, MD, PhD
Email:
Sub-Investigator
Facility:
Name:
UMC Utrecht
Address:
City:
Utrecht
Zip:
3508 GA
Country:
Netherlands
Contact:
Last name:
Veerle J Ruijters, MD
Phone:
0031639656920
Email:
v.j.ruijters-6@umcutrecht.nl
Contact backup:
Last name:
N Tolboom, MD, PhD
Phone:
003162878078
Email:
n.tolboom@umcutrecht.nl
Investigator:
Last name:
Nelleke Tolboom, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Tom J Snijders, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Veerle J Ruijters, MD
Email:
Sub-Investigator
Start date:
August 2024
Completion date:
December 2027
Lead sponsor:
Agency:
Veerle Ruijters
Agency class:
Other
Collaborator:
Agency:
ZonMw: The Netherlands Organisation for Health Research and Development
Agency class:
Other
Collaborator:
Agency:
Curium PET France
Agency class:
Industry
Source:
UMC Utrecht
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06480721
