Cutaneous Toxicity From ICI TherapyNCT04898751
Analysis of Reporting of Cutaneous Toxicities Associated With Immune Checkpoint Inhibitors
An observational study of Cutaneous Toxicity From ICI Therapy, run by Johns Hopkins University at 1 site in United States.
Trial summary
Immune checkpoint inhibitors (ICIs) are associated with a wide variety of cutaneous immune-related adverse events (cirAEs). These cirAEs are reported to be the most common immune-related adverse events (irAEs) and the first to appear. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cutaneous Toxicity From ICI Therapy
- What is being tested?
- Immune checkpoint inhibitor (ICI)
- How many people
- 2,214 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2008to 31 Aug 2020
- How long will I take part?
- 12 Years
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients treated with an immune checkpoint inhibitor for cancer.
Who may be able to join
- Treated with either Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33).
- Developed an adverse reaction that was submitted to a pharmacovigilance center and was determined to be related to aforementioned immune checkpoint inhibitors.
- Adverse reaction was determined to be within the System Organ Class (SOC) "Skin and subcutaneous disorder".
Who cannot join
- Adverse event was determined not to be immune-related (for example, infectious etiology) or was a symptom (e.g., edema).
- Adverse event developed before the administration of ICI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Care Center
Baltimore, Maryland, 21215
About this study
Immune checkpoint inhibitors (ICIs) are associated with a wide variety of cutaneous immune-related adverse events (cirAEs). These cirAEs are reported to be the most common immune-related adverse events (irAEs) and the first to appear. This study examines the appearance of cirAEs within the World Health Organization (WHO) pharmacovigilance database, VigiBase.
Read the detailed description
ICIs have revolutionized clinical oncologic care. The ICIs that are currently FDA approved fall into three main categories: those that block the cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4; ipilimumab), block the programmed cell death protein-1 (anti-PD-1; nivolumab, pembrolizumab, cemiplimab), and block the programmed cell death ligand-1 (anti-PD-L1; atezolizumab, avelumab, durvalumab) pathway. There is a considerable diversity of cirAEs that have been reported with these ICIs in both monotherapy and combination therapy.
VigiBase is the WHO pharmacovigilance database that monitors individual case safety reports associated with certain drugs. The largest database of its kind in the world, VigiBase is managed by the Uppsala Monitoring Center (UMC) in Sweden, and since its inception in 1967 has received over 19 million individual case safety reports (ICSRs) from over 130 contributing countries. In this study, the investigators examine the appearance of cutaneous immune related adverse events in the setting of immunotherapy within VigiBase.
- Conditions
- Cutaneous Toxicity From ICI Therapy
- Being tested
- Immune checkpoint inhibitor (ICI)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune checkpoint inhibitor (ICI)Drug
Also called Ipilimumab (Yervoy, L01XC11), Nivolumab (Opdivo, L01XC17), Pembrolizumab (Keytruda, L01XC18), Durvalumab (Imfinzi, L01XC28)
Immune checkpoint inhibitors included were targeting either PD-1, PD-L1 or CTLA-4, and had received FDA approval at the time of study (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33).
| Study group | Role | What they receive |
|---|---|---|
| Cutaneous toxicity | Patients who reported a cutaneous immune related adverse event following ICI initiation with appropriate chronology that indicates drug toxicity. Receives: Drug: Immune checkpoint inhibitor (ICI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cutaneous toxicity of ICIs
Number of reported adverse events associated with ICIs within the Systems Organ Class (SOC) "Skin and subcutaneous disorders" with one of the 7 FDA-approved ICIs Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), or Cemiplimab (L01XC33), alone or in any combination with each other.
Measured: From 01/01/2008 to 08/31/2020
Secondary outcomes (6)
Reporting odds ratio for monotherapy vs combination therapy
Reporting odds ratio for appearance of cirAEs, comparing the odds of appearance of cirAEs with monotherapy with PD-1, PD-L1, or CTLA-4 against combination therapy with a PD-1/PD-L1 and CTLA-4 agent.
Measured: From 01/01/2008 to 08/31/2020
Reporting odds ratio for differing monotherapy
Reporting odds ratio for appearance of cirAEs comparing monotherapy with PD1 or PD-L1 against monotherapy with CTLA-4
Measured: From 01/01/2008 to 08/31/2020
Co-occuring irAEs
Prevalence (%) of co-occuring irAEs within other organ systems (GI, endocrine/metabolic, pulmonary, cardiac, renal, hematologic, neurologic, rheumatologic, and ophthalmologic) with cirAEs.
Measured: From 01/01/2008 to 08/31/2020
Disproportionality assessment of cirAEs with ICIs
Information component (IC), a Bayesian confidence neural network propagation method devised by the Uppsala Monitoring Center, will determine significant disproportionate signal of cirAEs associated with ICIs if >0 at the bottom of the 95% confidence interval (IC025 > 0).
Measured: From 01/01/2008 to 08/31/2020
Indication
Prevalence (%) of malignancy types (such as melanoma, pulmonary, and renal cell carcinoma) for patients receiving ICIs and developing cirAEs.
Measured: From 01/01/2008 to 08/31/2020
Time to onset
Time to onset of cirAEs after ICI administration, measured in days.
Measured: From 01/01/2008 to 08/31/2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start1 Jan 2008
- Primary completion31 Aug 2020
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cutaneous Toxicity From ICI TherapyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 2,214 participants (actual)
- Target duration
- 12 Years
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shawn Kwatra, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04898751
- Sponsor's protocol ID
- JH IRB00210048
- Status last verified
- May 2021
- First submitted
- 19 May 2021
- Last updated
- 24 May 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Le TK, Brown I, Goldberg R, Taylor MT, Deng J, Parthasarathy V, Bordeaux ZA, Alphonse MP, Kwatra MM, Naranbhai V, Gusev A, Alhariri J, LeBoeuf NR, Reynolds KL, Cappelli LC, Naidoo J, Brahmer JR, Kang S, Semenov YR, Kwatra SG. Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study. J Invest Dermatol. 2022 Nov;142(11):2896-2908.e4. doi: 10.1016/j.jid.2022.04.020. Epub 2022 May 20.
PubMed 35605659
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Reporting of Cutaneous Toxicities Associated With Immune Checkpoint Inhibitors
- ClinicalTrials.gov ID
- NCT04898751
- Acronym / sponsor ID
- JH IRB00210048
- Conditions
- Cutaneous Toxicity From ICI Therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,214 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 1 Jan 2008 (actual)
- Primary completion
- 31 Aug 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 24 May 2021 (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) are associated with a wide variety of cutaneous immune-related adverse events (cirAEs). These cirAEs are reported to be the most common immune-related adverse events (irAEs) and the first to appear. This study examines the appearance of cirAEs within the World Health Organization (WHO) pharmacovigilance database, VigiBase.
Detailed description
ICIs have revolutionized clinical oncologic care. The ICIs that are currently FDA approved fall into three main categories: those that block the cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4; ipilimumab), block the programmed cell death protein-1 (anti-PD-1; nivolumab, pembrolizumab, cemiplimab), and block the programmed cell death ligand-1 (anti-PD-L1; atezolizumab, avelumab, durvalumab) pathway. There is a considerable diversity of cirAEs that have been reported with these ICIs in both monotherapy and combination therapy.
VigiBase is the WHO pharmacovigilance database that monitors individual case safety reports associated with certain drugs. The largest database of its kind in the world, VigiBase is managed by the Uppsala Monitoring Center (UMC) in Sweden, and since its inception in 1967 has received over 19 million individual case safety reports (ICSRs) from over 130 contributing countries. In this study, the investigators examine the appearance of cutaneous immune related adverse events in the setting of immunotherapy within VigiBase.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Target follow-up
- 12 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cutaneous toxicity | – | Drug: Immune checkpoint inhibitor (ICI)Patients who reported a cutaneous immune related adverse event following ICI initiation with appropriate chronology that indicates drug toxicity. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients treated with an immune checkpoint inhibitor for cancer.
Key inclusion criteria (3 listed)
- Treated with either Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33).
- Developed an adverse reaction that was submitted to a pharmacovigilance center and was determined to be related to aforementioned immune checkpoint inhibitors.
- Adverse reaction was determined to be within the System Organ Class (SOC) "Skin and subcutaneous disorder".
Key exclusion criteria (2 listed)
- Adverse event was determined not to be immune-related (for example, infectious etiology) or was a symptom (e.g., edema).
- Adverse event developed before the administration of ICI.
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 |
|---|---|---|
| Immune checkpoint inhibitor (ICI)Also: Ipilimumab (Yervoy, L01XC11), Nivolumab (Opdivo, L01XC17), Pembrolizumab (Keytruda, L01XC18), Durvalumab (Imfinzi, L01XC28)Immune checkpoint inhibitors included were targeting either PD-1, PD-L1 or CTLA-4, and had received FDA approval at the time of study (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33). | Drug | Cutaneous toxicity |
Primary outcome
Cutaneous toxicity of ICIs
Time frame: From 01/01/2008 to 08/31/2020
Number of reported adverse events associated with ICIs within the Systems Organ Class (SOC) "Skin and subcutaneous disorders" with one of the 7 FDA-approved ICIs Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), or Cemiplimab (L01XC33), alone or in any combination with each other.
6 secondary outcomes
Reporting odds ratio for monotherapy vs combination therapy
Time frame: From 01/01/2008 to 08/31/2020
Reporting odds ratio for differing monotherapy
Time frame: From 01/01/2008 to 08/31/2020
Co-occuring irAEs
Time frame: From 01/01/2008 to 08/31/2020
Disproportionality assessment of cirAEs with ICIs
Time frame: From 01/01/2008 to 08/31/2020
Indication
Time frame: From 01/01/2008 to 08/31/2020
Time to onset
Time frame: From 01/01/2008 to 08/31/2020
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 24 May 2021.
- Derived from this study: PubMed 35605659Le TK, Brown I, Goldberg R, Taylor MT, Deng J, Parthasarathy V, Bordeaux ZA, Alphonse MP, Kwatra MM, Naranbhai V, Gusev A, Alhariri J, LeBoeuf NR, Reynolds KL, Cappelli LC, Naidoo J, Brahmer JR, Kang S, Semenov YR, Kwatra SG. Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study. J Invest Dermatol. 2022 Nov;142(11):2896-2908.e4. doi: 10.1016/j.jid.2022.04.020. Epub 2022 May 20.
- Individual participant dataSharing planned: No
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.
Shawn Kwatra, MD principal investigator
Johns Hopkins University
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 Cutaneous Toxicity From ICI Therapy, run by Johns Hopkins University at 1 site in United States.
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 3 inclusion and 2 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 24 May 2021. 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 United States. 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?
Cutaneous toxicity of ICIs (time frame: From 01/01/2008 to 08/31/2020). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04898751, which also lists 1 linked publication.
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 24 May 2021.