Clinical trial NCT03216148: 18F-FET PET in Childhood Brain Tumours
Official title: A Prospective, Multicentre Trial on the Value of 18F-FET PET in the Post-therapeutic Evaluation of Childhood Brain Tumours
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain Neoplasm
Keywords: FET PET
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2017-07-13
Enrollment: 160
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All pediatric patients with brain Tumor receive a FET-PET Investigation in Addition to conventional MRI at the end of the first-line therapy. In case of Progression or Relapse patients may receive a second FET-PET Investigation in Addition to Routine surveillance MRI.
Primary purpose: DIAGNOSTIC

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Differentiating biologically active Tumor tissue from therapy related changes by using MRI (Magnetic Resonance Imaging) and FET PET
timeFrame: 3 years
Secondary outcomes:
measure: Sensitivity of FET-PET when differentiating biologically active Tumor tissue from therapy-related changes by using MRI (Magnetic Resonance Imaging) and FET PET
timeFrame: 3 years
measure: 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
timeFrame: 4 years
measure: 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
timeFrame: 4 years
measure: Safety data on FET-PET in children with brain tumors
timeFrame: 3 years
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Klinikum Augsburg, Onkologie
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, CVK, Onkologie
city: Bielefeld
country: Germany
facility: Evangelisches Krankenhaus Bielefeld gGmbH, Onkologie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Onkologie
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte gGmbH, Onkologie
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Onkologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Onkologie
city: Freiburg
country: Germany
facility: Klinik für Nuklearmedizin
city: Freiburg
country: Germany
facility: Klinik für Pädiatrische Hämatologie und Onkologie
city: Heidelberg
country: Germany
facility: Zentrum für Kinder- und Jugendmedizin, Angelika-Lautenschläger-Klinik, Onkologie
city: Jülich
country: Germany
facility: Institut für Neurowissenschaften und Medizin, Physik der medizinischen Bildgebung, Forschungszentrum Jülich, Nuklearmedizin
city: Köln
country: Germany
facility: Uniklinik Köln, Pädiatrische Onkologie
city: Köln
country: Germany
facility: Kliniken der Stadt Köln gGmbH
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz, Onkologie
city: München
country: Germany
facility: Kinderklinik München Schwabing, Onkologie
city: München
country: Germany
facility: Nuklearmedizinische Klinik und Poliklinik
city: Münster
country: Germany
facility: Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie
city: Münster
country: Germany
facility: Klinik für Nuklearmedizin
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart - Olgahospital, Onkologie
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart, Nuklearmedizin
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Onkologie
city: Würzburg
country: Germany
facility: Universitäts-Kinderklinik Würzburg
Study officials:
affiliation: Charite University, Berlin, Germany
name: Pablo Hernáiz Driever, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vivantes Klinikum
name: Michail Plotkin, MD
role: STUDY_CHAIR
References: