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出境医 / 临床实验 / Molecular Heterogeneity in Multilobar Low-grade Gliomas

Molecular Heterogeneity in Multilobar Low-grade Gliomas

Study Description
Brief Summary:

Low-grade diffuse glioma (GDBG) are rare tumors of young adults, whose ontogenesis is poorly understood. Patient management is based on the molecular profile defined by two molecular markers : mutations of the IDH genes and chromosomal 1p19q co-deletion. To date, the IDH and 1p19q statuses are determined on a single fragment collected from the tumor. In the case of GDBGs infiltrating several brain lobes, the sampling is done randomly on only one of the infiltrated lobes. An intra-tumoral heterogeneity of genetic alterations has been suggested and would impact management.

Phylogenetic analysis of genetic alterations found, by high throughput sequencing, in each lobe invaded by the same GDBG will make it possible to assess intra-tumoral heterogeneity and to discuss, at a fundamental level, the hypothesis of a single tumor site with secondary diffusion or that of the convergent progression of two or three distinct tumor sites. Clinically, understanding the ontogenesis of GDBGs will improve their management because of the known link between brain location, dominant molecular profile, and prognosis.


Condition or disease Intervention/treatment
Low-grade Diffuse Glioma Genetic: sequencing of the complete exome

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 8 participants
Observational Model: Case-Only
Time Perspective: Other
Official Title: Phylogenetic Analysis of Intra-tumor Molecular Heterogeneity on a Pilot Series of Diffuse Low-grade Multilobar Gliomas: Tumor Ontogenesis and Therapeutic Implications
Actual Study Start Date : June 24, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020
Arms and Interventions
Outcome Measures
Primary Outcome Measures :
  1. Genetic profile [ Time Frame: 12 month ]
    exhaustive high throughput sequencing of each of the 3 infiltrated lobes, followed by comparative phylogenetic analysis of the genetic profiles obtained in the 3 locations


Biospecimen Retention:   Samples With DNA
In this pilot study we chose the fronto-temporal-insular GDBG model to study the intra-tumoral heterogeneity of the low-grade gliomas by exhaustive high throughput sequencing of each of the 3 infiltrated lobes, followed by comparative phylogenetic analysis of the genetic profiles obtained in the 3 locations

Eligibility Criteria
Contacts and Locations
Tracking Information
First Submitted Date June 25, 2019
First Posted Date June 27, 2019
Last Update Posted Date December 3, 2019
Actual Study Start Date June 24, 2019
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 25, 2019)
Genetic profile [ Time Frame: 12 month ]
exhaustive high throughput sequencing of each of the 3 infiltrated lobes, followed by comparative phylogenetic analysis of the genetic profiles obtained in the 3 locations
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Molecular Heterogeneity in Multilobar Low-grade Gliomas
Official Title Phylogenetic Analysis of Intra-tumor Molecular Heterogeneity on a Pilot Series of Diffuse Low-grade Multilobar Gliomas: Tumor Ontogenesis and Therapeutic Implications
Brief Summary

Low-grade diffuse glioma (GDBG) are rare tumors of young adults, whose ontogenesis is poorly understood. Patient management is based on the molecular profile defined by two molecular markers : mutations of the IDH genes and chromosomal 1p19q co-deletion. To date, the IDH and 1p19q statuses are determined on a single fragment collected from the tumor. In the case of GDBGs infiltrating several brain lobes, the sampling is done randomly on only one of the infiltrated lobes. An intra-tumoral heterogeneity of genetic alterations has been suggested and would impact management.

Phylogenetic analysis of genetic alterations found, by high throughput sequencing, in each lobe invaded by the same GDBG will make it possible to assess intra-tumoral heterogeneity and to discuss, at a fundamental level, the hypothesis of a single tumor site with secondary diffusion or that of the convergent progression of two or three distinct tumor sites. Clinically, understanding the ontogenesis of GDBGs will improve their management because of the known link between brain location, dominant molecular profile, and prognosis.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
In this pilot study we chose the fronto-temporal-insular GDBG model to study the intra-tumoral heterogeneity of the low-grade gliomas by exhaustive high throughput sequencing of each of the 3 infiltrated lobes, followed by comparative phylogenetic analysis of the genetic profiles obtained in the 3 locations
Sampling Method Non-Probability Sample
Study Population resected tumor fragments, of the diagnosis of grade II glioma according to the 2016 WHO classification of brain tumors.
Condition Low-grade Diffuse Glioma
Intervention Genetic: sequencing of the complete exome
Once the pathological diagnosis is confirmed (WHO 2016), a tumor fragment will be selected and frozen for each lobe. DNA extraction will be performed for each fragment. The samples (4 different DNAs per GDBG corresponding to the DNA extracted from each of the 3 lobes and the blood DNA) will be sent to the Montpellier Genomix platform for sequencing of the complete exome.
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: June 25, 2019)
8
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Be over 18 years old.
  • Subject not opposed to participating in the study
  • Be scheduled in the operating room for the first surgery of a low-grade diffuse glioma presupposition on the basis of clinical and imaging criteria.
  • Confirmation, after histopathological analysis of the resected tumor fragments, of the diagnosis of grade II glioma according to the 2016 WHO classification of brain tumors.

Exclusion Criteria:

  • Patient minor, or major under legal protection, or unable to give consent.
  • Refusal to participate in the study.
  • Pathology diagnosis of grade III glioma according to WHO 2016 classification
  • Have received oncology treatment (chemotherapy and or chemotherapy) before the first surgery.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT04000048
Other Study ID Numbers RECHMPL18_0376
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University Hospital, Montpellier
Study Sponsor University Hospital, Montpellier
Collaborators Not Provided
Investigators Not Provided
PRS Account University Hospital, Montpellier
Verification Date June 2019