• FET PET in Differentiating Tumour Progression From Pseudoprogression in High Grade Glioma

  NCT06172595

  RecruitingInterventionalPhase 2Updated Dec 3, 2024
• Evaluating Tumor Pseudoprogression With FLT-PET and MRI

  NCT01105988

  TerminatedInterventionalEarly Phase 1Updated Jan 6, 2012
• Imaging and Biological Markers for Prediction and Identification of Glioblastoma Pseudoprogression: a Prospective Study.

  NCT06113705

  RecruitingInterventionalNot ApplicableUpdated Jan 31, 2025
• Application of FET-PET in Fusion With MRI in the Treatment of Glioblastoma Multiforme [TYR-GLIO]

  NCT06466031

  RecruitingInterventionalNot ApplicableUpdated Apr 17, 2026
• 18F-FET-PET/MRI vs Standard MRI Alone for Stereotactic RadioTherapy Planning for High Grade Brain Gliomas

  NCT06499831

  Unknown statusInterventionalNot ApplicableUpdated May 25, 2025
• FET-PET/MRI Based Treatment Planning for Glioblastoma Multiforme in Post-Surgical Patients (FET-TREAT)

  NCT06451042

  CompletedObservationalUpdated Dec 18, 2025

ClinicalTrials.gov ID

NCT06480721

Lead Sponsor

Veerle RuijtersOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Not Applicable

Enrollment

144Estimated

Last Update Posted

Jun 28, 2024Actual

Start Date

Aug 2024Estimated

Primary Completion Date

Dec 2027Estimated

Completion Date

Dec 2027Estimated

Official Title

FET-PET-Guided Management of Pseudoprogression in Glioblastoma

Brief 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.

• Glioblastoma
• Radionecrosis of Brain

• Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

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

Primary Purpose

Diagnostic

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Veerle RuijtersOTHER

Collaborators

ZonMw: The Netherlands Organisation for Health Research and DevelopmentOTHER

Curium PET FranceINDUSTRY

Dylan.Henssen@radboudumc.nl

s.veldhuijzenvanzanten@erasmusmc.nl

M.vos@haaglandenmc.nl

v.j.ruijters-6@umcutrecht.nl0031639656920