Tumor Characteristics in Patients With Paraneoplastic Neurological Syndromes (PNS) (GenePNS)

May 28, 2019 updated by: Hospices Civils de Lyon

Genomic Profile and Tumor Immune Attack in Paraneoplastic Neurological Syndromes (PNS)

Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer that can affect any part of the central or peripheral nervous system.

PNS occurs at the intersection between immune system and the tumor, where a combination of genetical and environmental factors may play a role.

Mechanisms leading to immune tolerance breakdown and autoimmunity in PNS remain largely unknown, and this reflects in an unsatisfactory repertoire of treatments available. Moreover, a better understanding of the biological mechanisms underlying PNS would allow a more precise identification of the modalities that permit PNS patients to have a better oncological prognosis than cancer patient without PNS, with obvious repercussions in clinical oncology.

To this effect, an extremely innovative approach involves directly exploring the tumoral tissue of patients suffering from specific PNS via genomic and transcriptomic analysis.

The study team hypothesizes that antigen ectopic expression by tumour cells may contribute to the generation of PNS.

In the present study, the investigators will analyze the salient features of tumors associated with PNS, namely the histological and immune cells infiltrate characteristics, their transcriptomic profile, and mutational status of involved antigens.

Study Overview

Study Type

Observational

Enrollment (Anticipated)

980

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Lyon, France
        • Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with cancer and suspected Paraneoplastic neurological syndrome (PNS) whose sample was sent for analysis at the Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Lyon, France, for paraneoplastic antibody study and then stored at the biobank Neurobiotec.

Description

Inclusion Criteria:

  • presence of well characterized antibodies in serum or cerebrospinal fluid;
  • histologically proven cancer with available tumour sample;
  • Paraneoplastic neurological syndrome (PNS) diagnosis according to the international guidelines;
  • Age: at least 18 years old.

Exclusion Criteria:

  • Absence of complete clinicopathological data

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cancer patients with Paraneoplastic neurological syndromes

Cancer patients with Paraneoplastic neurological syndromes presenting various autoimmune anomalies:

  • Anti-Hu also known as anti-Neuron specific cell Nuclear Antibodies (anti-ANNA1) (350 patients), uncommon form of brain inflammation associated with an underlying cancer
  • anti-Yo (130 patients), antibody associated with paraneoplastic cerebellar degeneration
  • anti-Ma2 (50 patients), antibody associated with paraneoplastic encephalitis
  • anti-N-methyl-d-aspartate (NMDA) Receptor (350 patients), autoimmune disorder in which antibodies attack N-methyl-D-aspartate-type glutamate receptors
  • anti-gamma-aminobutyric acid-B (GABAb) receptor (35 patients), autoimmune disorder in which antibodies attack gamma-aminobutyric acid-B receptors
  • anti-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor (15 patients), autoimmune disorder in which antibodies attack alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors
  • without antibodies (50 patients).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of mutations in cancer genes coding for onconeural proteins and inflammatory response mediators.
Time Frame: 36 months
Genetic alterations in tumors associated with Paraneoplastic neurological syndromes (PNS)
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of different immune cells in the tumor's immune infiltrate
Time Frame: 36 months
Histological immune infiltrate characteristics
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 1, 2019

Primary Completion (ANTICIPATED)

January 1, 2022

Study Completion (ANTICIPATED)

January 1, 2022

Study Registration Dates

First Submitted

April 26, 2019

First Submitted That Met QC Criteria

May 23, 2019

First Posted (ACTUAL)

May 28, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 30, 2019

Last Update Submitted That Met QC Criteria

May 28, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • GenePNS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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