Clinical trial NCT05942872: CICLOPS Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.
Official title: Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Paraneoplastic Syndromes
Keywords: ICIs
NirAEs
paraneoplastic neurological syndromes
Neurological toxicity
immune checkpoint inhibitors
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2023-07-12
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with cancer treated with ICIs who experienced CTCAE grade ≥ 3 neurological toxicity (NirAEs)

Brief 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.


Eligibility criteria: 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..)

Primary outcomes:
measure: Prognostic factors in patients with NirAEs
timeFrame: Baseline (onset of NirAE) and 1 year.
Secondary outcomes:
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites autoimmunes
Study officials:
References: