Using the Epitranscriptome to Diagnose and Treat Gliomas

NCT06575452 | Not Yet Recruiting

• 2 other identifiers: PROICM 2023-05 EPIID-RCB : 2023-A02360-45
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 2

Brief Summary

Diffuse gliomas are among the most common tumors of the central nervous system, with high morbidity and mortality and very limited therapeutic possibilities. The diffuse glioma are characterized by significant variability in terms of age at diagnosis, histological and molecular features, classification, ability to transform to a higher grade and/or to disseminate in the brain, response to treatment and patient outcome. One of the main challenges in the management of diffuse gliomas is related to tumor heterogeneity within the same subgroup. Establishing an accurate tumor classification is of paramount importance for selecting personalized therapy or avoiding unnecessary treatment. At present, the main diagnostic methods for detecting gliomas are based on histopathological features and mutation detection. Yet difficulties remain, due to tumor heterogeneity and sampling bias for tumors obtained from small biopsies. In particular, grade 2 (low-grade) and grade 3 (high-grade) gliomas cannot be easily distinguished, as intra-tumoral tumor grade heterogeneity is not uncommon in patients treated with extensive surgical resection. Another challenge in the field of gliomas is longitudinal monitoring of disease progression, which is currently mainly based on repeated brain Magnetic Resonance Imaging (MRI). New tools to detect tumor changes before the onset of imaging changes would be useful. Several genetic, epigenetic, metabolic and immunological profiles have been established for gliomas. Recently, the world of RiboNucleic Acid (RNA) has emerged as a promising area to explore for cancer therapy, especially since the (re)discovery of RNA chemical modifications. To date, more than 150 types of post-transcriptional modifications have been reported on various RNA molecules. This complex landscape of chemical marks embodies a new, invisible code that governs the post-transcriptional fate of RNA: stability, splicing, storage, translation.

Conditions

Glioma

Outcome Measures

Primary Outcomes (4)

• Sensitivity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in blood for patients in cohort 1.

  Sensitivity of a test corresponds to its ability to give a positive result when the hypothesis is verified.

  At baseline, 3 months, 9 months and 18 months

• Specificity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in blood for patients in cohort 1.

  Specificity measures the ability of a test to give a negative result when the hypothesis is not verified.

  At baseline, 3 months, 9 months and 18 months

• Positive Predictive Value (PPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in blood for patients in cohort 1.

  Predictive value of a test is the probability of a condition being present as a function of the test result.

  At baseline, 3 months, 9 months and 18 months

• Negative Predictive Value (NPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in blood for patients in cohort 1.

  Negative predictive value is the probability that the condition is not present when the test is negative.

  At baseline, 3 months, 9 months and 18 months

Secondary Outcomes (21)

• Sensitivity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in urine for patients in cohort 1.

  At baseline, 3 months, 9 months and 18 months

• Specificity of RNA-modified nucleoside expression marks for glioma diagnosis vs controls in urine for patients in cohort 1.

  At baseline, 3 months, 9 months and 18 months

• Positive Predictive Value (PPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in urine for patients in cohort 1.

  At baseline, 3 months, 9 months and 18 months

• Negative Predictive Value (NPV) of modified nucleoside expression marks for the diagnosis of glioma vs. controls in urine for patients in cohort 1.

  At baseline, 3 months, 9 months and 18 months

• Progression-free survival

  Time from histological diagnosis to date of progression according to the Response Assessment in Neuro-Oncology Criteria (RANO 2.0) or death from any cause, assessed up to 18 months.

Study Arms (3)

Cohort 1

OTHER

Prospective cohort: 80 patients and 20 healthy volunteers * Grade 2 mutated Isocitrate Dehydrogenase (IDH) glioma: 20 patients * IDH mutated grade 3 glioma: 20 patients * Glioblastoma (GBM), IDH wild-type: 40 patients

Diagnostic Test: Blood, urine and tumoral tissue samples

Cohort 2

OTHER

Retrospective cohort: 120 patients * Grade 2 mutated Isocitrate Dehydrogenase (IDH) glioma: 40 patients * IDH mutated grade 3 glioma: 40 patients * Glioblastoma, IDH wild-type: 40 patients

Diagnostic Test: Tumoral tissue samples

Cohort 3

OTHER

Spatial epitranscriptomic cohort: 8 patients (grade 2 mutated Isocitrate Dehydrogenase (IDH ) glioma with grade 3 or grade 4 focus

Diagnostic Test: Tumoral tissue samples

Interventions

Blood, urine and tumoral tissue samples DIAGNOSTIC_TEST

Blood, urine and tumoral tissue samples

Cohort 1

Tumoral tissue samples DIAGNOSTIC_TEST

tumoral tissue samples

Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male / female over 18 years of age,
• Surgery (tumor resection) scheduled at Montpellier University Hospital for suspected, diffuse glioma, confirmed on tissue sample: IDH mutated grade 2 glioma (excluding tumors with a focus of grade 3 or 4 glioma), IDH mutated grade 3 glioma or GBM, IDH wild-type,
• No history of treatment (surgery, radiotherapy or chemotherapy) for glioma,
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures,
• Patient has given express written informed consent prior to any study procedure,
• Patient affiliated to a French health insurance.

You may not qualify if:

• Patients whose regular follow-up is impossible for psychological, family, social or geographical reasons,
• Patients under guardianship, curatorship or safeguard of justice,
• Pregnant and/or breast-feeding patient (information gathered from the medical file, as part of the patient's standard medical care and follow-up),
• Histo-molecular diagnosis of grade 4 IDH-mutated astrocytoma,
• For grade 2 gliomas, presence within the tumor of one or more higher-grade sites (3 or 4).

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead
• National Cancer Institute, France: collaborator

Study Sites (2)

Insitut Régional du Cancer de Montpellier

Montpellier, Hérault, 34298, France

Location

CHU Montpellier - Hôpital St Eloi

Montpellier, 34090, France

Location

Related Publications (13)

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  PMID: 28855326 BACKGROUND

• Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016 Jun;131(6):803-20. doi: 10.1007/s00401-016-1545-1. Epub 2016 May 9.

  PMID: 27157931 BACKGROUND

• Posti JP, Bori M, Kauko T, Sankinen M, Nordberg J, Rahi M, Frantzen J, Vuorinen V, Sipila JO. Presenting symptoms of glioma in adults. Acta Neurol Scand. 2015 Feb;131(2):88-93. doi: 10.1111/ane.12285. Epub 2014 Sep 28.

  PMID: 25263022 BACKGROUND

• Darlix A, Rigau V, Fraisse J, Goze C, Fabbro M, Duffau H. Postoperative follow-up for selected diffuse low-grade gliomas with WHO grade III/IV foci. Neurology. 2020 Feb 25;94(8):e830-e841. doi: 10.1212/WNL.0000000000008877. Epub 2020 Jan 22.

  PMID: 31969465 BACKGROUND

• Pedeutour-Braccini Z, Burel-Vandenbos F, Goze C, Roger C, Bazin A, Costes-Martineau V, Duffau H, Rigau V. Microfoci of malignant progression in diffuse low-grade gliomas: towards the creation of an intermediate grade in glioma classification? Virchows Arch. 2015 Apr;466(4):433-44. doi: 10.1007/s00428-014-1712-5. Epub 2015 Jan 21.

  PMID: 25861023 BACKGROUND

• Barbieri I, Kouzarides T. Role of RNA modifications in cancer. Nat Rev Cancer. 2020 Jun;20(6):303-322. doi: 10.1038/s41568-020-0253-2. Epub 2020 Apr 16.

  PMID: 32300195 BACKGROUND

• Macari F, El-Houfi Y, Boldina G, Xu H, Khoury-Hanna S, Ollier J, Yazdani L, Zheng G, Bieche I, Legrand N, Paulet D, Durrieu S, Bystrom A, Delbecq S, Lapeyre B, Bauchet L, Pannequin J, Hollande F, Pan T, Teichmann M, Vagner S, David A, Choquet A, Joubert D. TRM6/61 connects PKCalpha with translational control through tRNAi(Met) stabilization: impact on tumorigenesis. Oncogene. 2016 Apr 7;35(14):1785-96. doi: 10.1038/onc.2015.244. Epub 2015 Aug 3.

  PMID: 26234676 BACKGROUND

• Relier S, Amalric A, Attina A, Koumare IB, Rigau V, Burel Vandenbos F, Fontaine D, Baroncini M, Hugnot JP, Duffau H, Bauchet L, Hirtz C, Rivals E, David A. Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics. Anal Chem. 2022 Sep 6;94(35):11967-11972. doi: 10.1021/acs.analchem.2c01526. Epub 2022 Aug 23.

  PMID: 35998076 BACKGROUND

• Relier S, Ripoll J, Guillorit H, Amalric A, Achour C, Boissiere F, Vialaret J, Attina A, Debart F, Choquet A, Macari F, Marchand V, Motorin Y, Samalin E, Vasseur JJ, Pannequin J, Aguilo F, Lopez-Crapez E, Hirtz C, Rivals E, Bastide A, David A. FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell. Nat Commun. 2021 Mar 19;12(1):1716. doi: 10.1038/s41467-021-21758-4.

  PMID: 33741917 BACKGROUND

• Amalric A, Bastide A, Attina A, Choquet A, Vialaret J, Lehmann S, David A, Hirtz C. Quantifying RNA modifications by mass spectrometry: a novel source of biomarkers in oncology. Crit Rev Clin Lab Sci. 2022 Jan;59(1):1-18. doi: 10.1080/10408363.2021.1958743. Epub 2021 Sep 2.

  PMID: 34473579 BACKGROUND

• Wen PY, van den Bent M, Youssef G, Cloughesy TF, Ellingson BM, Weller M, Galanis E, Barboriak DP, de Groot J, Gilbert MR, Huang R, Lassman AB, Mehta M, Molinaro AM, Preusser M, Rahman R, Shankar LK, Stupp R, Villanueva-Meyer JE, Wick W, Macdonald DR, Reardon DA, Vogelbaum MA, Chang SM. RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults. J Clin Oncol. 2023 Nov 20;41(33):5187-5199. doi: 10.1200/JCO.23.01059. Epub 2023 Sep 29.

  PMID: 37774317 BACKGROUND

• Moons KG, Altman DG, Reitsma JB, Ioannidis JP, Macaskill P, Steyerberg EW, Vickers AJ, Ransohoff DF, Collins GS. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015 Jan 6;162(1):W1-73. doi: 10.7326/M14-0698.

  PMID: 25560730 BACKGROUND

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  PMID: 2868172 BACKGROUND

MeSH Terms

Conditions

Glioma

Interventions

Blood Specimen Collection; Urination

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Amélie DARLIX, MD

  Institut régional du Cancer de Montpellier (ICM)

  STUDY CHAIR

Central Study Contacts

Aurore MOUSSION

CONTACT

467612446; aurore.moussion@icm.unicancer.fr

Emmanuelle TEXIER

CONTACT

467613102; emmanuelle.texier@icm.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 28, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Access to study data upon written detailed request sent to the institute of Montpellier Cancer (ICM), following publication and until 5 years after publication of summary data.
• Access Criteria: The data shared will be limited to that required for independent mandated verification of the published results, the applicant will need authorization from ICM for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (2)