CICLOPS Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.

Paraneoplastic Syndromes Clinical Trial

— LOPF - NIRAES  

Official title:

Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05942872
• Other study ID #: 474
• Status: Completed
• Start date: April 1, 2021
• Est. completion date: September 15, 2021

Study information

• Verified date: July 2023
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Immune-checkpoint inhibitors (ICIs) have radically changed the therapy of cancer in recent years. ICIs promote antitumor immune response inhibiting one of the following immune checkpoints: cytotoxic T-lymphocyte antigen-4 (CTLA-4; ipilimumab), programmed death-1 (PD-1: pembrolizumab, nivolumab, and cemiplimab), and programmed death ligand-1 (PD-L1: atezolizumab, durvalumab, and avelumab). Despite the desired effect as cancer treatment, ICIs can break immune tolerance to self-antigens and induce specific toxicities known as immune-related adverse events (irAEs), that may affect both peripheral and central nervous system (Neurological immune mediated adverse events, NirAEs). The pathogenic mechanisms underlying NirAEs are probably heterogeneous, as reflected by the variety of clinical phenotypes and severity.

NirAEs are rare, but there is some concern that the incidence may increase in the next future, in particular because ICIs are being used more and more for cancers commonly associated with paraneoplastic neurological syndromes (e.g. small-cell lung cancer). Moreover, NirAEs are usually severe, and often fatal. Indeed, irAEs-related complications are the most common cause of death among these patients. On the other hand, these patients usually have a good tumor response to immunotherapy. There is some evidence that irAEs may predict ICIs efficacy and consequently NirAE surivors are likely to have longer life expectancy than non-NirAE patients.

Therefore, it is of utmost importance to better characterize the long-term outcomes of NirAE patients in terms of neurologic disability and mortality, and to identify predictors of severe NirAEs. So far, only few studies with sufficient follow-up have been published on the topic, and they included only small number of patients.

The aims of our study is to characterize the main clinical and paraclinical features of NirAEs in a large cohort of NirAE patients, to assess long-term outcomes and to identify prognostic factors. This study will help define new guidelines regarding NirAE prediction and management.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: September 15, 2021
• Est. primary completion date: July 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients who developed NirAEs (grade severity equal or more than 3 according to CTCAE)

Exclusion Criteria:

• alternative better explanation for neurological symptoms (cancer progression, carcinomatous meningitis, complications of other treatments..)

Related Conditions & MeSH terms

• Neurotoxicity Syndromes
• Paraneoplastic Syndromes

Intervention

Other:
• This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.
This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.

Locations

Country	Name	City	State
France	Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites autoimmunes	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prognostic factors in patients with NirAEs	Evaluation of residual neurological disability as assessed by the modified Rankin scale (mRS); 0 - No symptoms.; - No significant disability. Able to carry out all usual activities, despite some symptoms.; - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; - Moderate disability. Requires some help, but able to walk unassisted.; - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; - Dead.	Baseline (onset of NirAE) and 1 year.