Evaluation of Diagnostic Performances of 18F-FDOPA PET KInetics

Glioma Clinical Trial

— KING  

Official title:

Evaluation of Diagnostic Performances of 18F-FDOPA PET KInetics as Biomarkers for the Improvement of Care of MRI Non-contrast Enhanced Gliomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05512403
• Other study ID #: 2020PI126
• Status: Recruiting
• Phase: Phase 3
• Start date: June 13, 2023
• Est. completion date: October 30, 2026

Study information

• Verified date: July 2023
• Source: Central Hospital, Nancy, France
• Contact: VERONIQUE ROCH, MSc
• Phone: 0383154276
• Email: v.roch[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: October 30, 2026
• Est. primary completion date: December 12, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• PET/CT with 18F-DOPA
A 18F-FDOPA PET exam is then performed (acquisition of 30 minutes in List Mode format) according to the French guidelines for PET neuro-oncological indications (Verger et al. Med Nuc, 2020, (5)). Patient preparation and acquisition: 4 hours of fasting No carbidopa premedication 2 MBq / kg of 18F-FDOPA Dynamic acquisition in List Mode format for 30 min starting simultaneously with the patient's injection Low dose scanner for attenuation correction

Locations

Country	Name	City	State
France	CHRU Nancy	Vandoeuvre les Nancy cedex

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	the sensitivity, specificity, predictive positive value (PPV) and negative predictive value (NPV) of the 18F-FDOPA kinetic TTP parameter, to characterise aggressive lesions within suspected LGGs with no contrast enhancement on MRI at the initial diagnosis.	24 months
Secondary	To assess the diagnostic performances of 18F-FDOPA "slope", to characterise aggressive lesions	Sensitivity, specificity, Positive Predictive Value and Negative Predicitive Value of the 18F-FDOPA kinetic "slope" parameter	24 months
Secondary	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	Sensitivity, specificity, positive predictive and negative predictive values of the 18F-FDOPA conventional parameters and/or radiomics analysis and the kinetic parameter.	24 months
Secondary	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	Proportion of aggressive lesions expressed as an instantaneous prevalence and its 95% confidence interval of the total number of suspected LGGs without any contrast enhancement on MRI examined at initial diagnosis and referred for biopsy or surgery within the following 6 months.; enhancement	24 months
Secondary	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	Number of patients who need to be diagnosed with 18F-FDOPA kinetic parameter TTP to identify an aggressive lesion within the suspected LGG population that do not exhibit any contrast enhancement on MRI at initial diagnosis and that undergo biopsy/surgery, defined as: 1/ [% of aggressive lesions detected with the 18F-FDOPA Time-To-Peak parameter].	24 months