FET-PET-Guided Management of Pseudoprogression in Glioblastoma

NCT ID: NCT06480721

Last Updated: 2024-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-31

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Glioblastoma Radionecrosis of Brain

Keywords

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Glioblastoma [¹⁸F] FET PET Tumor progression Pseudoprogression Unnecessary interventions Health-related quality of life Healthcare costs

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomised in equal proportions between two arms: the investigational arm and the control arm.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Clinical management is based on the index MRI and an additional [¹⁸F] FET-PET together

Group Type EXPERIMENTAL

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

Intervention Type OTHER

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.

Standard of care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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

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.

Intervention Type OTHER

Eligibility Criteria

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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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Curium PET France

INDUSTRY

Sponsor Role collaborator

Veerle Ruijters

OTHER

Sponsor Role lead

Responsible Party

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Veerle Ruijters

Medical researcher

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Tom J Snijders, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Nelleke Tolboom, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

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Amsterdam UMC

Amsterdam, , Netherlands

Site Status

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status

UMC Groningen

Groningen, , Netherlands

Site Status

Maastricht UMC

Maastricht, , Netherlands

Site Status

Radboud UMC

Nijmegen, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

Haaglanden MC

The Hague, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Countries

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Netherlands

Central Contacts

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Veerle J Ruijters, MD

Role: CONTACT

Phone: 0031639656920

Email: [email protected]

Nelleke Tolboom, MD, PhD

Role: CONTACT

Phone: 003162878078

Email: [email protected]

Facility Contacts

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Elsmarieke M van de Giessen, MD, PhD

Role: primary

Dylan JH Henssen, MD, PhD

Role: primary

Sophie EM Veldhuijzen van Zanten, MD, PhD

Role: primary

Maaike J Vos, MD, PhD

Role: primary

Veerle J Ruijters, MD

Role: primary

N Tolboom, MD, PhD

Role: backup

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Other Identifiers

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10390022210022

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NL86008.041.24

Identifier Type: -

Identifier Source: org_study_id