FET-PET-Guided Management of Pseudoprogression in Glioblastoma

NCT06480721 | Not Yet Recruiting

• 2 other identifiers: NL86008.041.2410390022210022
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 8

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.

Conditions

Glioblastoma; Radionecrosis of Brain

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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

  at six months

• 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.

  at twelve weeks

• 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.

  at twelve weeks

• 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.

  at twelve weeks

• 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.

  at twelve weeks

Secondary Outcomes (9)

• Cost-effectiveness

  at six months

• Cost-effectiveness

  at six months

• Time-to-diagnosis

  During the study period (but expected within three months)

• Overall survival

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

• Number of unnecessary treatment cycles

  at six months

Study Arms (2)

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

EXPERIMENTAL

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

Standard of care

NO INTERVENTION

Interventions

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Veerle Ruijters: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Curium PET France: collaborator

Study Sites (8)

Amsterdam UMC

Amsterdam, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

UMC Groningen

Groningen, Netherlands

Location

Maastricht UMC

Maastricht, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Haaglanden MC

The Hague, Netherlands

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

Related Publications (20)

• 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.

  PMID: 21393407 BACKGROUND

• 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.

  PMID: 15248032 BACKGROUND

• 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.

  PMID: 25411133 BACKGROUND

• 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.

  PMID: 26008606 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 27106405 BACKGROUND

• 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.

  PMID: 19269895 BACKGROUND

• 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.

  PMID: 29260225 BACKGROUND

• 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.

  PMID: 36502457 BACKGROUND

• 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.

  PMID: 31541032 BACKGROUND

• 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.

  PMID: 34185076 BACKGROUND

• 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.

  PMID: 38181810 BACKGROUND

• 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.

  PMID: 25015058 BACKGROUND

• 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.

  BACKGROUND

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

  BACKGROUND

• iMTA. iMTA Medical Consumption Questionnaire. Available from: https://www.imta.nl/questionnaires/imcq/.

  BACKGROUND

• European Medicines Agency (Science Medicines Health). 2015. Guideline on adjustment for baseline covariates in clinical trials. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-adjustment-baseline-covariates-clinical-trials_en.pdf

  BACKGROUND

• ZonMw. Budget Impact Analyses in de praktijk - Leidraad en rekentool. Februari 2020. Available from: https://www.zonmw.nl/sites/zonmw/files/typo3-migrated-files/Budget_Impact_Analyses_in_de_praktijk_-_Leidraad_en_rekentool.pdf

  BACKGROUND

• Netherlands Commission on Radiation Dosimetry. Human Exposure to Ionising Radiation for Clinical and Research Purposes: Radiation Dose & Risk Estimates. 2020.

  BACKGROUND

• Ruijters VJ, Snijders TJ, van der Pol JAJ, van de Giessen EM, Niers JM, Broen MPG, Anten MM, van Zanten SEMV, Geurts M, Arens AIJ, Henssen DJHA, Gijtenbeek JM, van der Meulen M, Sijben AEJ, Ghariq E, Vos MJ, Tim J, Bosma IB, Stormezand GN, Frederix GWJ, Dankbaar JW, Robe PA, Verhoeff JJC, de Vos FYFL, Lam MGEH, Ten Ham RMT, Tolboom N. [18F]FET PET-Guided management of pseudoprogression in glioblastoma (FET POPPING): the study protocol for a diagnostic randomized clinical trial. Trials. 2025 Jun 17;26(1):208. doi: 10.1186/s13063-025-08921-8.

  PMID: 40528226 DERIVED

MeSH Terms

Conditions

Glioblastoma; Disease Progression

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tom J Snijders, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Nelleke Tolboom, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veerle J Ruijters, MD

CONTACT

0031639656920; v.j.ruijters-6@umcutrecht.nl

Nelleke Tolboom, MD, PhD

CONTACT

003162878078; n.tolboom@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical researcher

Model Details: Participants will be randomised in equal proportions between two arms: the investigational arm and the control arm.

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 28, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 28, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (8)