Paraneoplastic SyndromesLOPF - NIRAESNCT05942872
CICLOPS Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.
An observational study of Paraneoplastic Syndromes, run by Hospices Civils de Lyon at 1 site in France.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paraneoplastic Syndromes
- What is being tested?
- This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.
- How many people
- 90 participants
- Where
- 1 siteFrance
- Study dates
- 1 Apr 2021to 15 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with cancer treated with ICIs who experienced CTCAE grade ≥ 3 neurological toxicity (NirAEs)
Who may be able to join
- patients who developed NirAEs (grade severity equal or more than 3 according to CTCAE)
Who cannot join
- alternative better explanation for neurological symptoms (cancer progression, carcinomatous meningitis, complications of other treatments..)
Trial locations and contacts
1 site in 1 country.
France1 site
Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites autoimmunes
Lyon, 69677
About this study
Official title: Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.
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.
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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.
- Conditions
- Paraneoplastic Syndromes
- Being tested
- This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.
- Keywords
- ICIs, NirAEs, paraneoplastic neurological syndromes, Neurological toxicity, immune checkpoint inhibitors
- Medical subject headings
- Paraneoplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.Other
This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.
| Study group | Role | What they receive |
|---|---|---|
| NirAEs, grade ≥ 3 according to CTCAE | Patients treated with ICIs who developed neurologic syndromes consistent with NirAEs, of grade ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) Receives: Other: This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (onset of NirAE) and 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2023
- Study start1 Apr 2021
- Primary completion15 Jul 2021
- Study completion15 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paraneoplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05942872
- Sponsor's protocol ID
- 474
- Acronym
- LOPF - NIRAES
- Status last verified
- Jul 2023
- First submitted
- 6 Mar 2023
- Last updated
- 12 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.
- ClinicalTrials.gov ID
- NCT05942872
- Acronym / sponsor ID
- LOPF - NIRAES / 474
- Conditions
- Paraneoplastic Syndromes
- Keywords
- ICIs, NirAEs, paraneoplastic neurological syndromes, Neurological toxicity, immune checkpoint inhibitors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 15 Jul 2021 (actual)
- Study completion
- 15 Sep 2021 (actual)
- First posted
- 12 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NirAEs, grade ≥ 3 according to CTCAE | – | Other: This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.Patients treated with ICIs who developed neurologic syndromes consistent with NirAEs, of grade ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with cancer treated with ICIs who experienced CTCAE grade ≥ 3 neurological toxicity (NirAEs)
Key inclusion criteria (1 listed)
- patients who developed NirAEs (grade severity equal or more than 3 according to CTCAE)
Key exclusion criteria (1 listed)
- alternative better explanation for neurological symptoms (cancer progression, carcinomatous meningitis, complications of other treatments..)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | NirAEs, grade ≥ 3 according to CTCAE |
Primary outcome
Prognostic factors in patients with NirAEs
Time frame: Baseline (onset of NirAE) and 1 year.
Evaluation of residual neurological disability as assessed by the modified Rankin scale (mRS) 0 - No symptoms. 1. - No significant disability. Able to carry out all usual activities, despite some symptoms. 2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. - Moderate disability. Requires some help, but able to walk unassisted. 4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. - Dead.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Paraneoplastic Syndromes, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prognostic factors in patients with NirAEs (time frame: Baseline (onset of NirAE) and 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2023.