In Vivo Succinate Detection After External Beam Radiation Therapy in SDHx- Paragangliomas (RADIOSUCCES)

Evolution of Succinate Accumulation Detected in Vivo by Spectroscopic Magnetic Resonance Imaging (1H-SRM) After External Beam Radiation Therapy in SDHx-mutated Patients With Cervical Paragangliomas

Qualitative and quantitative biomarker of response to radiotherapy is needed in paragangliomas. We aim at assessing the added value of 1H-SRM for the evaluation of early response to EBR therapy in patients with cervical SDHx PGL.

Study Overview

• Status: Recruiting
• Conditions: Paraganglioma of Head and Neck
• Intervention / Treatment: Diagnostic test: 1H-Spectroscopy MRI

Detailed Description

Paragangliomas (PGL) are rare neuroendocrine tumors inherited in 40% of cases. SDHx genes (SDHA, SDHB, SDHC, SDHD), encoding the 4 subunits of the mitochondrial enzyme succinate dehydrogenase (SDH), are the most frequently involved.

Accumulation of succinate, the substrate for SDH, is a very specific biomarker for these mutations. Recently, we have demonstrated the feasability of detecting and quantifying succinate in tumors in vivo, by magnetic resonance spectroscopy (1H-SRM).

Patients carrying these mutations frequently develop cervical PGL for which the treatment of choice is external beam radiation therapy (EBR).

The objective of this project is to determine the feasibility of using 1H-SRM for the evaluation of early response to EBR therapy in patients with cervical SDHx PGL.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charlotte LUSSEY-LEPOUTRE, PhD; Phone Number: +33142178370; Email: charlotte.lussey@inserm.fr
• Study Contact Backup: Name: Malha BERRAH, MSc; Phone Number: +33156095822; Email: malha.berrah@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Hopital Lariboisiere
    • Contact: Philippe HERMAN, Dr; Phone Number: +33147711111; Email: philippe.herman@aphp.fr
  • Paris, France, 75015
    • Recruiting
    • Hopital Europeen Georges Pompidou
    • Contact: Laurence AMAR, PhD; Phone Number: +33156093771; Email: laurence.amar@aphp.fr
  • Paris, France, 75013
    • Recruiting
    • Hôpital Pitié-Salpétrière
    • Contact: Charlotte LUSSEY-LEPOUTRE, Dr; Phone Number: +33142178370; Email: charlotte.lussey@inserm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Signed informed consent
• Patient with cervical PGL with planning of treatment with EBR
• Patient with an SDHx mutation or unknown genetic status
• Patient affiliated to a social security scheme

Exclusion Criteria:

• Pregnant woman
• Contraindication to MRI (implantable device, etc.)
• Impossibility of lying down without movement for 45 minutes (hyperalgesic patient, claustrophobia, etc.)
• PPGL having previously been the subject of local (excluding surgery) or systemic treatment
• PPGL <1 cm longest axis
• Patient under guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Assigned Intervention; Addition to the cervical angio-MRI, of a sequence of 1H-SRM 3T (SUCCESS) centered on the lesion studied, performed according to the following parameters: PRESS asymmetric monovoxel "PROBE", TE 144 ms, TR 2500 ms, 768 or 1024 medium.	Diagnostic test: 1H-Spectroscopy MRI; PRESS asymetric monovoxel " PROBE ", TE 144 ms, TR 2500 ms, 768 or 1024 averages

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disappearance of succinate accumulation at M12	Absence of succinate accumulation detected in vivo by 1H-SRM, in cervical PGLs with SDHx mutations, at 12 months after EBR, reviewed by 2 independant experts blinded to all other clinical and genetics data.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disapperance of succinate accumulation at M3	Absence of succinate accumulation detected in vivo by 1H-SRM, in cervical PGLs with SDHx mutations, at 3 months after EBR, reviewed by 2 independant experts blinded to all other clinical and genetics data.	3 months
Performance of cervical MRI at M3 and M12 after EBR	Reference diagnostic for response assessed by MRI at 3 months and 12 months after EBR: 1/ Complete response : tumour disappearance ; 2/ Partial response : decrease by at least 30% of tumour volume and no clinical symptomatology worsening ; 3/ stable : stability of tumour size and no clinical symptomatology worsening; 4/ Progression : increase by at least 20% of tumour volume and/or clinical symptomatological worsening	12 months
Performance of PET/CT at M12 after EBR	PERCIST criteria (PET response criteria in solid tumors) assessed by PET/CT at 3 months and 12 months after EBR	12 months
Metastatic evolution or death at M12	Occurence of an event related to the disease during 12 months follow-up (metastatic evolution of the disease or death). Metastases diagnostic is assessed remotely by presence in chromaffin tissue (http://www.sfendocrino.org/article/599/recommandations)	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Society for Endocrinology
• Investigators: Principal Investigator: Laurence AMAR, PhD, Hopital Europeen Georges-Pompidou

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 27, 2020
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (ACTUAL): October 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 22, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Paraganglioma,SDHx genes, 1H-Spectroscopy MRI
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Paraganglioma
• Other Study ID Numbers: APHP200281; 2020-A00397-32 (OTHER: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared.
• IPD Sharing Time Frame: Two years after the last publication

IPD Sharing Access Criteria

Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No