Clinical trial NCT05512403: Evaluation of Diagnostic Performances of 18F-FDOPA PET KInetics
Official title: Evaluation of Diagnostic Performances of 18F-FDOPA PET KInetics as Biomarkers for the Improvement of Care of MRI Non-contrast Enhanced Gliomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Glioma
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2022-08-23
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients presenting with brain lesions that lack contrast enhancement on MRI, that are suspected to be LGGs and that are referred for biopsy or surgery within the following 6 months will be eligible for the study.
Primary purpose: DIAGNOSTIC

Brief summary: the investigators hypothesise that 18F-FDOPA PET kinetic parameters are good biomarkers to characterise suspected LGG brain lesions that exhibit no contrast on MRI, for identifying aggressive lesions. These parameters could constitute diagnostic biomarkers for this indication. This new diagnostic tool could enhance patient care in the short term in an evolving pathology affecting socially active subjects with a poor prognosis

Detailed description: Diffuse low-grade gliomas (LGGs) without any contrast enhancement on MRI are rare (15% of gliomas, 700 cases/year in France), have a poor prognosis (median overall survival from 5 to 15 years) and affect young, socially active subjects (median age 40 years). Among these lesions, 30% present with high grade histopathological criteria or with poor prognostic molecular characteristics, according to the 2021 WHO Classification of Tumors of the Central Nervous System (lack of IDH \[Isocitrate DeHydrogenase\] mutation, CDKN2A/B deletion). These high-grade types of tumours progress within 6 months and their diagnosis and management represent a public health issue. Moreover, the care of LGG patients is currently not standardised.

Although treatment is based on surgery and the complete excision of the lesion, as far as this is possible, and/or first-line chemotherapy ±radiotherapy, the optimal time to begin treatment remains controversial.

Aggressive forms should be diagnosed as soon as possible to allow immediate surgery to improve survival, whilst strategies allowing the maintenance of an optimal quality of life, more often with functional surgery alone, are recommended for non-aggressive forms. The main hurdle to standardised patient management is the lack of amenable non-invasive biomarkers to identify aggressive LGG forms.

18F-FDOPA positron emission tomography (PET) is promising to diagnose initial gliomas with conventional Standardised-Uptake-Value (SUV) parameters. Our team recently demonstrated the potential of 18F-FDOPA PET kinetics to better characterise gliomas. Two parameters are determined from the 30-minute dynamic acquisition curve of the tumour: the time-to-peak SUV (TTP), and the SUV slope. In our previous studies, limited by their monocentric and retrospective nature, molecular characteristics were mainly predicted by TTP: long TTP for an IDH-mutation and short TTP for IDH-wildtype tumours. A prospective multicentric study is needed to confirm our preliminary results in a specific population of suspected LGGs without any contrast enhancement on MRI.

The investigator hypothesise that 18F-FDOPA PET kinetic parameters are biomarkers which lead to improved care because they characterise aggressive forms of gliomas exhibiting no contrast on MRI.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 75 years old
* WHO general condition ≤2
* Identification of a unifocal brain tumour at the initial diagnosis with no contrast in the MRI and suspected to be a LGG, with biopsy/surgery envisaged within 6 months of the PET scan
* MRI performed a maximum of 3 weeks before inclusion and comprising the conventional morphological sequences (T1, T1 sequences with injection of contrast agent and T2 FLAIR).
* Subject affiliated to or beneficiary of a social security plan
* Subject having received complete information on the organisation of the research and having signed the informed consent form.

Exclusion Criteria:

* Multifocal brain lesions
* Contraindication to 18F-FDOPA PET
* Pregnant, parturient women or nursing mothers under Article L1121-5
* Women of childbearing age who do not have effective contraception under Article L1121-5
* Monitoring not possible
* Persons deprived of their liberty by a judicial or administrative decision under Article 1121-8, persons undergoing psychiatric treatment under Articles L. 3212-1 and L. 3213-1.
* Patients cannot simultaneously participate in an interventional research trial for the duration of the KING study

Primary outcomes:
measure: To assess diagnostic performances of 18F-FDOPA PET (Positon Emission Tomography) Time-To-Peak in suspected LGGs without MRI -contrast enhancement for characterisation of aggressive lesions
timeFrame: 24 months
Secondary outcomes:
measure: To assess the diagnostic performances of 18F-FDOPA "slope", to characterise aggressive lesions
timeFrame: 24 months
measure: To assess the diagnostic performances of 18F-FDOPA SUV static conventional parameters and/or radiomics analyses associated with TTP kinetic parameter, to characterise aggressive lesions
timeFrame: 24 months
measure: To assess, in patients suspected to have a non-contrast enhanced glioma at diagnosis the prevalence of aggressive forms within the suspected LGGs without any MRI contrast
timeFrame: 24 months
measure: To assess, in patients suspected to have a non-contrast enhanced glioma at diagnosis the clinical impact of the 18F-FDOPA PET (positon emission tomography) Time-To-Peak parameter
timeFrame: 24 months
Other outcomes:
Locations:
city: Vandoeuvre les Nancy cedex
country: France
facility: CHRU Nancy
Study officials:
affiliation: CHRU Nancy
name: Antoine VERGER, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP salpêtrière PARIS
name: Aurélie KAS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHM Marseille
name: Eric GUEDJ, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de cancérologie Strasbourg Europe
name: Caroline BUND, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eugène MARQUIS Nantes
name: Florence LEJEUNE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospices Civils de Lyon
name: Anthelme FLAUS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Grenoble
name: Nicolas De LEIRIS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU de Brest
name: Solène QUERELLOU, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Nimes
name: Laurent COLLOMBIER, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Tours
name: Maria RIBEIRO, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Lille
name: Franck SEMAH, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHR Metz
name: Merwan GINET, MD
role: PRINCIPAL_INVESTIGATOR
References: