Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06314607 |
| Other study ID # |
APHP220498 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 26, 2024 |
| Est. completion date |
March 2034 |
Study information
| Verified date |
April 2024 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Marc Sanson, Prof |
| Phone |
01 42 16 03 91 |
| Email |
marc.sanson[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Primary and secondary brain tumors, the leading cause of death from cancer before the age of
35, represent a complex and heterogeneous group of pathologies with a generally poor
prognosis. Knowledge of these tumors has made enormous strides thanks to access to biological
samples, leading to a much more robust, reliable and precise histo-pronostic classification,
but also, increasingly, to the identification of theranostic targets.
Despite these advances, there is a real need to refine diagnostic and prognostic
classification, identify the biological mechanisms involved in the formation and progression
of these pathologies, develop new targeted strategies, and devise minimally invasive
follow-up methods (liquid biopsies).
In addition, certain non-tumoral brain lesions (e.g. malformations) can be similarly
classified according to their molecular and mutational profile.
This project aims to make a decisive contribution to these objectives.
Description:
Over the past 15 years, knowledge of these tumors has increased exponentially, thanks to the
genomic revolution (high-throughput sequencing, methylome analysis), which has improved their
classification, defining homogeneous prognostic, predictive and even theranostic groups
(BRAF, FGFR, NTRK). This knowledge has only progressed thanks to access to tumor samples, but
also to constitutional DNA and liquid biopsies.
The histo-pronostic classification of these tumors is constantly evolving, as evidenced by
the new WHO 2021 version, which integrates more and more molecular markers for diagnosis (in
which the team participated), and considerably modifies nosological frameworks. This process
began with the 2007 classification, which was purely morphological and particularly
unsatisfactory, with over 30% inter-observer diagnostic discordance, and the 2016 version has
considerably clarified the classification of grade 2 and 3 gliomas, by integrating biomarkers
that are now unavoidable, such as 1p19q codeletion and IDH1 and IDH2 mutation: however, it
has taken several years for these markers to be routinely performed and managed. The
extremely rapid evolution of diagnostic criteria is illustrated by the c-impact now
initiative, which has regularly revisited the classification of primary brain tumours, and
gliomas in particular, in the light of the most recent publications, and on which the 2021
classification is based: however, certain data are still fragile and criticized because they
are based on limited series (for example, the definition of grade 2 gliomas, reclassified as
"molecular glioblastomas".
Glioblastoma and other diffuse gliomas are incurable, lethal diseases that are resistant to
conventional treatments (radiotherapy, chemotherapy). Compared with other cancers, the number
of effective treatments and therefore treatment lines available is limited. The longitudinal
study of these diseases is essential to understanding the mechanisms of resistance to
treatment and identifying new vulnerabilities. Our team actively contributes to this
research, for which tumor samples at initial diagnosis, but also at recurrence and possibly
post-mortem are invaluable.
Given its strengths, our team can now make a decisive contribution to improving diagnosis and
prediction in the management of primary brain tumors.
First and foremost, the team represents Europe's leading center for the management of glioma
patients. Between 10% and 15% of patients with primary brain tumors in France are treated in
Neuro-oncology at La Salpêtrière.
Beyond the diagnostic aspect, high-throughput sequencing techniques have made it possible to
identify anomalies that can be used in oncology. However, these are still rarely detected in
gliomas. Only a very limited number of markers, included in the WHO2016 classification, which
we helped to identify, are now part of the "standard" management of these patients. The rest
are part of research. However, we have recently shown that a broader search for actionable
abnormalities carried out in specific studies, has enabled patients to benefit from
personalized therapies with a real gain in survival, but access is still restricted via the
Seqoia program, to a small number of patients.
In conclusion, there is a real need to refine diagnostic and prognostic classification,
identify new targeted strategies, and develop minimally invasive follow-up methods (liquid
biopsies).
Some lesions, however, are not tumoral in nature, but rather malformative, such as cerebral
dysplasia or vascular malformations. Interestingly, somatic mutations are also found at the
origin of these lesions, making it possible to classify them, and above all to propose
treatments targeting these alterations. As these non-tumoral lesions are subject to a
diagnostic and sometimes therapeutic strategy similar to tumors, and as our team has
developed real expertise in this field, and above all as it is not always possible to
distinguish, pre-operatively, between a malformative lesion and a tumor, we have broadened
the search, and retain the term "lesion" in the patient information and consent form.
