18F-FET PET in Childhood Brain Tumours

A Prospective, Multicentre Trial on the Value of 18F-FET PET in the Post-therapeutic Evaluation of Childhood Brain Tumours

FET PET 2010 is a prospective, multicentre trial aiming to evaluate the additional benefit of FET PET in the assessment of remission after first line therapy and during follow-up

Study Overview

• Status: Unknown
• Conditions: Brain Neoplasm
• Intervention / Treatment: Diagnostic test: FET-PET

Detailed Description

2.1 Primary objective The main objective is to evaluate the relative benefit of FET PET in comparison to the MRI in differentiating biologically active tumour tissue from therapy-related changes in paediatric brain tumours after first line therapy (Δ specificityFET PET to specificityMRT) 2.2 Secondary Objectives To assess sensitivity of FET PET in comparison with the sensitivity of MRI (Δ sensitivityFET PET to sensitivityMRT) To assess the positive and negative predictive values (PPV, NPV) of FET PET in comparison with the PPV and NPV of MRI (Δ PPVFET PET to PPVMRT, Δ NPVFET PET to NPVMRT) To evaluate specificity, sensitivity, PPV, and NPV by SUVratio analyses of FET PET data To evaluate the potential of FET PET for non-invasive tumour grading (WHO I/II vs. III/IV) by kinetic studies when histology is available To assess adverse events and toxicity profile

2.3 Endpoints (Standard of truth1) 2.3.1 Primary Endpoint The primary endpoint is an event free survival of the follow-up period of 24 (12) months after first line therapy (confirmed by clinical and neuroradiological assessment) or the confirmed diagnosis of progression or recurrence of brain tumour tissue (confirmed by histology or clinical and neuroradiological assessment).

The follow-up period for patients with a low risk of tumour recurrence after first line therapy, i.e. astrocytoma WHO grade I-II, oligodendroglioma WHO grade I-II, germ cell tumour, choroid plexus tumour, craniopharyngioma will be 24 months.

The follow-up period for patients with a high risk of tumour recurrence after first line therapy, i.e. astrocytoma WHO grade III-IV, oligodendroglioma WHO grade III-IV, medulloblastoma, supratentorial PNET, AT/RT and other high-grade tumour lesions will be 12 months.

2.3.2 Secondary Endpoints To assess the secondary objectives of the FET PET 2010 study, the investigators will determine event free survival of the follow-up period of 24 (12) months after first line therapy (confirmed by clinical and neuroradiological assessment) or the confirmed diagnosis of progression or recurrence of brain tumour tissue (confirmed by histology or clinical and neuroradiological assessment).

Histopathological characteristics of recurrent tumours (WHO grade I-IV) Safety and Toxicity (evolution according to CTCEA v3.0 criteria): the NCI Common Terminology Criteria for Adverse Events v3.0 is a descriptive terminology, that is used for Adverse Event (AE) reporting. A grading scale is provided for each AE term. Attached is a selection of categories, which are required to assess safety and toxicity of FET PET examinations.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Uwe Behrens, PhD; Email: uwe.behrens@charite.de
• Study Contact Backup: Name: Ramona Stöckl; Email: ramona.stoeckl@charite.de

Study Locations

• Germany
  • Augsburg, Germany, 86156
    • Not yet recruiting
    • Klinikum Augsburg, Onkologie
    • Contact: Michael Frühwald, Prof. Dr.
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Universitätsmedizin Berlin, CVK, Onkologie
    • Contact: Pablo Hernaiz Driever, MD; Phone Number: +49 30 450 666173; Email: pablo.hernaiz@charite.de
  • Bielefeld, Germany, 33617
    • Not yet recruiting
    • Evangelisches Krankenhaus Bielefeld gGmbH, Onkologie
    • Contact: Norbert Jorch, Dr.
  • Bonn, Germany, 53113
    • Recruiting
    • Universitätsklinikum Bonn, Onkologie
    • Contact: Dagmar Dilloo, Prof. Dr.
    • Contact: Stefan Schönberger, MD
  • Bremen, Germany, 25117
    • Not yet recruiting
    • Klinikum Bremen-Mitte gGmbH, Onkologie
    • Contact: Arnulf Pekrun, Prof. Dr.
  • Düsseldorf, Germany, 40225
    • Not yet recruiting
    • Universitätsklinikum Düsseldorf, Onkologie
    • Contact: Stefan Balzer, MD
    • Contact: Julia Hauer, MD
  • Essen, Germany, 45122
    • Recruiting
    • Universitätsklinikum Essen, Onkologie
    • Contact: Gudrun Fleischhack, Prof. Dr.
    • Contact: Michael Schündeln, MD
    • Sub-Investigator: Thorsten Pöppel, MD
    • Sub-Investigator: Michael Forsting, Prof.
  • Freiburg, Germany, 79106
    • Recruiting
    • Klinik fur Nuklearmedizin
    • Contact: Philipp T Meyer, Prof. Dr.; Phone Number: +49 761 270 39160; Email: sek.nuklearmedizin@uniklinik-freiburg.de
    • Contact: Timo Spehl, MD
  • Freiburg, Germany, 79106
    • Recruiting
    • Klinik für Pädiatrische Hämatologie und Onkologie
    • Contact: Charlotte Niemeyer, Prof. Dr.
    • Contact: Jochen Rösler, Prof. Dr.
  • Heidelberg, Germany, 69120
    • Recruiting
    • Zentrum für Kinder- und Jugendmedizin, Angelika-Lautenschläger-Klinik, Onkologie
    • Contact: Olaf Witt, Prof. Dr.
    • Contact: Till Milde, MD
    • Sub-Investigator: Uwe Haberkorn, Prof. Dr.
    • Sub-Investigator: Sabine Haufe, MD
  • Jülich, Germany, 52425
    • Recruiting
    • Institut für Neurowissenschaften und Medizin, Physik der medizinischen Bildgebung, Forschungszentrum Jülich, Nuklearmedizin
    • Contact: Karl-Josef Langen, Prof. Dr.
  • Köln, Germany
    • Recruiting
    • Kliniken der Stadt Koln gGmbH
    • Contact: Aram Prokop, MD
    • Contact: Stephan Lobitz, MD
    • Sub-Investigator: Manol Velev, MD
  • Köln, Germany, 50937
    • Recruiting
    • Uniklinik Köln, Pädiatrische Onkologie
    • Contact: Thorsten Simon, Prof. Dr.
    • Contact: Barbara Hero, MD
  • Mainz, Germany, 55131
    • Recruiting
    • Universitätsklinikum Mainz, Onkologie
    • Contact: Jörg Faber, Dr.
    • Contact: Alexandra Russo, MD
    • Sub-Investigator: Matthias Miederer, MD
  • München, Germany, 80804
    • Not yet recruiting
    • Kinderklinik München Schwabing, Onkologie
    • Contact: Julia Köhle, Dr.
    • Contact: Irene Teichert von Lüttichau, MD
  • München, Germany, 81675
    • Not yet recruiting
    • Nuklearmedizinische Klinik und Poliklinik
    • Contact: Stefan Förster, Dr.
  • Münster, Germany, 48149
    • Not yet recruiting
    • Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie
    • Contact: Ronald Sträter, MD
    • Contact: Cornelius Kerl
  • Münster, Germany, 48149
    • Not yet recruiting
    • Klinik fur Nuklearmedizin
    • Contact: Matthias Weckesser, Prof. Dr.
    • Contact: Kambiz Rahar
  • Stuttgart, Germany, 70174
    • Recruiting
    • Klinikum Stuttgart - Olgahospital, Onkologie
    • Contact: Stefan Bielack, Prof. Dr.
    • Contact: Stephanie Knirsch, MD
  • Stuttgart, Germany, 70174
    • Recruiting
    • Klinikum Stuttgart, Nuklearmedizin
    • Contact: Gabriele Pöpperl, Prof. Dr.
    • Contact: Marcus Nicolai, MD
  • Tübingen, Germany, 72076
    • Not yet recruiting
    • Universitätsklinikum Tübingen, Onkologie
    • Contact: Martin Ebinger, Dr.
    • Contact: Carl-Philipp Schwarze, MD
  • Würzburg, Germany, 97060
    • Not yet recruiting
    • Universitäts-Kinderklinik Würzburg
    • Contact: Matthias Eyrich, Prof. Dr.
    • Contact: Paul-Gerhardt Schlegel, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent (given by the parents as legal representatives of the patients and given by the patients)
• Completion of the first line therapy according to the current HIT-protocols (Current and subsequent paediatric primary brain tumour treatment studies approved by GPOH)
• Fully evaluable MRI at the end of first line therapy as confirmed by the reference centre of neuroradiology (Prof. Dr. M. Warmuth-Metz, Würzburg)
• Histology of primary brain tumour confirmed by local and reference centre of Neuropathology (Prof. Dr. T. Pietsch) except for patients where tumour diagnosis is confirmed by the reference centre of neuroradiology, i.e. NF-1 and confirmed LGG or patient with diffuse intrinsic pontine glioma
• Laboratory requirements prior to enrolment: Serum creatinine: within normal limits; AST, ALT: not more than 10 x above normal limits
• Age at inclusion: 1 year to 17 years
• Children below the age of 12 years are included as 2 of 3 paediatric patients with a brain tumour are younger than 12 years. Furthermore, young age is a known negative risk factor for different histological entities. Thus, this group is the most likely to benefit from the results of this study
• In all patients with reproductive potential, a pregnancy must be excluded by a pregnancy test before FET PET investigation
• Highly effective contraception in women with reproductive potential (defined as pearl index < 1) during study participation and follow up time
• No participation in other clinical trials according to AMG with the same clinical indication over the course of the FET PET 2010 study

Exclusion Criteria:

• Presence of solid non-CNS tumours or leukaemia
• MRI at completion of first line therapy that does not meet standard quality criteria for evaluation as defined by the reference centre for neuroradiology of the HITNetzwerk (Würzburg, Prof. Warmuth-Metz);
• Known allergic reactions or drug intolerance to contrast agents
• Patients according to § 88 StrhlSchV
• Pregnancy or breast-feeding
• Women (adolescents) of childbearing potential without highly effective contraception (PEARL-Index < 1%), for example ParaGard IntraUterineDevice (IUD), Mirena IUD, Implants, Depo Provera Injections;
• Persons who are detained officially or legally to an official institute

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FET-PET; All participating patients will receive a FET PET-scan with intravenous O-(2-[18F]Fluoroethyl)-L-Tyrosine parallel to the routine MRI at the end of the first line therapy (restaging) according to the HIT-protocol Second FET PET: In case of suspected tumour recurrence or progression within the follow-up period of 24 (12) months, the participating patient will receive a second FET PET-scan (parallel to an MRI)

Diagnostic test: FET-PET; All participating patients will receive a FET PET-scan parallel to the routine MRI at the end of the first line therapy (restaging) according to the HIT-protocol Second FET PET: In case of suspected tumour recurrence or progression within the follow-up period of 24 (12) months, the participating patient will receive a second FET PET-scan (parallel to an MRI); Other Names: O-(2-[18F]Fluoroethyl)-L-Tyrosine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differentiating biologically active Tumor tissue from therapy related changes by using MRI (Magnetic Resonance Imaging) and FET PET	The main objective is to evaluate the relative benefit of FET PET in comparison to the MRI in differentiating residual biologically active tumour tissue from therapy related changes in paediatric brain tumours after first line therapy (Δ specificityFET PET to specificityMRT)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of FET-PET when differentiating biologically active Tumor tissue from therapy-related changes by using MRI (Magnetic Resonance Imaging) and FET PET	To assess sensitivity of FET PET in comparison with the sensitivity of MRI (Δ sensitivityFET PET to sensitivityMRT)	3 years
Assessment of the predictive value of FET-PET when differentiating biologically active Tumor tissue from therapy-related changes by using MRI (Magnetic Resonance Imaging) and FET PET	(PPV, NPV) of FET PET in comparison with the PPV and NPV of MRI (Δ NPVFET PET to NPVMRT)	4 years
Assessment of Tumor grading by FET-PET when differentiating biologically active Tumor tissue from therapy-related changes by using MRI (Magnetic Resonance Imaging) and FET PET	SUVratio analyses of FET PET data to allow for Analysis of Tumor grading when histological results are available	4 years
Safety data on FET-PET in children with brain tumors	To assess adverse events and toxicity Profile using Common Terminology Criteria for Adverse Events, CTCAE v4.03	3 years

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Pablo Hernáiz Driever, MD, Charite University, Berlin, Germany; Study Chair: Michail Plotkin, MD, Vivantes Klinikum

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: FET PET
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: FET PET 2010; 2008-005786-60 (EudraCT Number)