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AzTrials

GlioblastomaFET-POPPINGNCT06480721

FET-PET-Guided Management of Pseudoprogression in Glioblastoma

A study testing Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan in people with Glioblastoma and Radionecrosis of Brain, run by Veerle Ruijters at 8 sites in Netherlands.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Radionecrosis of Brain
What is being tested?
Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
8 sitesNetherlands
Study dates
Aug 2024to Dec 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Veerle J Ruijters, MD contact

0031639656920

v.j.ruijters-6@umcutrecht.nl

Nelleke Tolboom, MD, PhD contact

003162878078

n.tolboom@umcutrecht.nl

8 sites in 1 country

Netherlands8 sites

  • Amsterdam UMC

    Amsterdam

    Elsmarieke M van de Giessen, MD, PhD, E.m.vandegiessen@amsterdamumc.nl

    Elsmarieke M van de Giessen, MD, PhD

  • Medisch Spectrum Twente

    Enschede

  • UMC Groningen

    Groningen

  • Maastricht UMC

    Maastricht

  • Radboud UMC

    Nijmegen

    Dylan JH Henssen, MD, PhD, Dylan.Henssen@radboudumc.nl

    Dylan JH Henssen, MD, PhD

  • Erasmus MC

    Rotterdam

    Sophie EM Veldhuijzen van Zanten, MD, PhD, s.veldhuijzenvanzanten@erasmusmc.nl

    Sophie EM Veldhuijzen van Zanten, MD, PhD

  • Haaglanden MC

    The Hague

    Maaike J Vos, MD, PhD, M.vos@haaglandenmc.nl

    Maaike J Vos, MD, PhD

  • UMC Utrecht

    Utrecht, 3508 GA

    Veerle J Ruijters, MD, 0031639656920, v.j.ruijters-6@umcutrecht.nl

    N Tolboom, MD, PhD, 003162878078, n.tolboom@umcutrecht.nl

Other trials in Netherlands

About this study

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:

Read more
  • 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.

Read the 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.

Being tested
Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan
Keywords
Glioblastoma, [¹⁸F] FET PET, Tumor progression, Pseudoprogression, Unnecessary interventions, Health-related quality of life, Healthcare costs
Medical subject headings
Glioblastoma, Disease Progression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    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.

Study groups in NCT06480721
Study groupRoleWhat they receive
Clinical management is based on the index MRI and an additional [¹⁸F] FET-PET togetherExperimentalNot described
Receives: Other: Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan
Standard of careNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite score of proportion (0-100%) of patients undergoing unnecessary interventions.

    Determination of 'unnecessary interventions' will be done retrospectively, by the researchers and the treating physician.

    An 'unnecessary intervention' is defined as:

    • Biopsy or debulking for diagnostic uncertainty and/or with pseudoprogression as the final pathological diagnosis
    • The administration of one or more cycles of (temozolomide) chemotherapy as continued treatment for presumed pseudoprogression, in cases with a final diagnosis of tumor progression
    • The administration of one or more doses of bevacizumab for presumed pseudoprogression, in cases with a final diagnosis of tumor progression

    Measured: at six months

  2. Health-related quality of life: general

    This will be reported by the questionnaire EQ5D. The EQ5D is a generic utility questionnaire which allows for comparison of quality of life between indications, and is considered the golden standard by the Dutch National Heath Care Institute. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at twelve weeks

  3. Health-related quality of life: brain tumor specific

    This will be reported by the questionnaire European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module (EORTC-QLQ-BN20). The EORTC-QLQ-BN20 is a brain tumor specific questionnaire and is a reliable tool to capture changes in specific health domains for this population. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at twelve weeks

  4. Health-related quality of life: productivity

    This will be reported by the questionnaire iMTA Productivity Cost Questionnaire (iPCQ). The iPCQ questionnaire measures productivity losses and is applicable to national and international studies.

    Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at twelve weeks

  5. Health-related quality of life: medical consumption

    This will be reported by the questionnaire iMTA Medical Consumption Questionnaire (iMCQ). The iMCQ questionnaire is an instrument for measuring medical consumption. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at twelve weeks

Secondary outcomes (9)

  1. Cost-effectiveness

    Expressed in Quality Adjusted Life Years (QALY). The results of the cost utility analysis will be combined with observed and extrapolated uptake to estimate the budget impact over several relevant time horizons.

    Measured: at six months

  2. Cost-effectiveness

    Expressed in Incremental Cost Effectiveness Ratio's (ICERs). The results of the cost utility analysis will be combined with observed and extrapolated uptake to estimate the budget impact over several relevant time horizons.

    Measured: at six months

  3. Time-to-diagnosis

    Defined as index MRI to eventual management, including watchful waiting

    Measured: During the study period (but expected within three months)

  4. Overall survival

    Defined from index MRI until death (patients who are still alive at the end of the study will be censored)

    Measured: Through study completion (expected median of less than 1.5 year)

  5. Number of unnecessary treatment cycles

    Chemotherapy

    Measured: at six months

  6. Health-related quality of life: general

    This will be reported by the questionnaire EQ5D. The EQ5D is a generic utility questionnaire which allows for comparison of quality of life between indications, and is considered the golden standard by the Dutch National Heath Care Institute. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at six weeks and six months

  7. Health-related quality of life: brain tumor specific

    This will be reported by the questionnaire European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module (EORTC-QLQ-BN20). The EORTC-QLQ-BN20 is a brain tumor specific questionnaire and is a reliable tool to capture changes in specific health domains for this population. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at six weeks and six months

  8. Health-related quality of life: productivity

    This will be reported by the questionnaire iMTA Productivity Cost Questionnaire (iPCQ). The iPCQ questionnaire measures productivity losses and is applicable to national and international studies.

    Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at six weeks and six months

  9. Health-related quality of life: medical consumption

    This will be reported by the questionnaire iMTA Medical Consumption Questionnaire (iMCQ). The iMCQ questionnaire is an instrument for measuring medical consumption. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.

    Measured: at six weeks and six months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2024
  2. Study startAug 2024 (estimated)
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomised in equal proportions between two arms: the investigational arm and the control arm.
Masking
None (open label)
Enrolment
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06480721
Sponsor's protocol ID
NL86008.041.24
Other IDs
10390022210022
Acronym
FET-POPPING
Status last verified
Jun 2024
First submitted
17 Jun 2024
Last updated
28 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hygino da Cruz LC Jr, Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 2011 Dec;32(11):1978-85. doi: 10.3174/ajnr.A2397. Epub 2011 Mar 10.

    PubMed 21393407

  • Popperl G, Gotz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004 Nov;31(11):1464-70. doi: 10.1007/s00259-004-1590-1. Epub 2004 Jul 10.

    PubMed 15248032

  • Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, Reifenberger G, Kebir S, Dorn F, Blau T, Herrlinger U, Hau P, Ruge MI, Kocher M, Goldbrunner R, Fink GR, Drzezga A, Schmidt M, Langen KJ. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015 Apr;42(5):685-95. doi: 10.1007/s00259-014-2959-4. Epub 2014 Nov 20.

    PubMed 25411133

  • Galldiks N, Stoffels G, Filss C, Rapp M, Blau T, Tscherpel C, Ceccon G, Dunkl V, Weinzierl M, Stoffel M, Sabel M, Fink GR, Shah NJ, Langen KJ. The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro Oncol. 2015 Sep;17(9):1293-300. doi: 10.1093/neuonc/nov088. Epub 2015 May 24.

    PubMed 26008606

  • Richtlijnendatabase. Onderscheiden tumorprogressie en therapie-effect bij gliomen. 2020; Available from: https://richtlijnendatabase.nl/richtlijn/gliomen/follow-up_na_gliomen/onderscheiden_tumorprogressie_en_therapie-effect_bij_gliomen.html.

  • Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, la Fougere C, Pope W, Law I, Arbizu J, Chamberlain MC, Vogelbaum M, Ellingson BM, Tonn JC. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol. 2016 Sep;18(9):1199-208. doi: 10.1093/neuonc/now058. Epub 2016 Apr 21.

    PubMed 27106405

  • Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9.

    PubMed 19269895

  • Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran D, Brem S, Hottinger A, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

    PubMed 29260225

  • Singnurkar A, Poon R, Detsky J. 18F-FET-PET imaging in high-grade gliomas and brain metastases: a systematic review and meta-analysis. J Neurooncol. 2023 Jan;161(1):1-12. doi: 10.1007/s11060-022-04201-6. Epub 2022 Dec 11.

    PubMed 36502457

  • de Zwart PL, van Dijken BRJ, Holtman GA, Stormezand GN, Dierckx RAJO, Jan van Laar P, van der Hoorn A. Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis. J Nucl Med. 2020 Apr;61(4):498-504. doi: 10.2967/jnumed.119.233809. Epub 2019 Sep 20.

    PubMed 31541032

  • Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106.

    PubMed 34185076

  • Albert NL, Galldiks N, Ellingson BM, van den Bent MJ, Chang SM, Cicone F, de Groot J, Koh ES, Law I, Le Rhun E, Mair MJ, Minniti G, Ruda R, Scott AM, Short SC, Smits M, Suchorska B, Tolboom N, Traub-Weidinger T, Tonn JC, Verger A, Weller M, Wen PY, Preusser M. PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0): a report of the RANO group. Lancet Oncol. 2024 Jan;25(1):e29-e41. doi: 10.1016/S1470-2045(23)00525-9.

    PubMed 38181810

  • Chow R, Lao N, Popovic M, Chow E, Cella D, Beaumont J, Lam H, Pulenzas N, Bedard G, Wong E, DeAngelis C, Bottomley A. Comparison of the EORTC QLQ-BN20 and the FACT-Br quality of life questionnaires for patients with primary brain cancers: a literature review. Support Care Cancer. 2014 Sep;22(9):2593-8. doi: 10.1007/s00520-014-2352-7.

    PubMed 25015058

  • Nederland, Z. Richtlijn voor het uitvoeren van economische evaluaties in de gezondheidszorg (versie 2024). 2024; Available from: https://www.zorginstituutnederland.nl/over-ons/publicaties/publicatie/2024/01/16/richtlijn-voor-het-uitvoeren-van-economische-evaluaties-in-de-gezondheidszorg.

  • iMTA. iMTA Productivity Cost Questionnaire. Available from: https://www.imta.nl/questionnaires/ipcq/.

Questions about this trial

What is this clinical trial studying?

A study testing Clinical management based on the index MRI and an additional [¹⁸F] FET PET scan in people with Glioblastoma and Radionecrosis of Brain, run by Veerle Ruijters at 8 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Veerle J Ruijters, MD (0031639656920, v.j.ruijters-6@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite score of proportion (0-100%) of patients undergoing unnecessary interventions. (time frame: at six months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06480721, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2024.

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