CancerICI-DISCOVERNCT04268368
Immune Related-adverse Events in Patients Receiving Immune Checkpoint Inhibitors
An observational study of Cancer and Lung Cancer, run by Università Politecnica delle Marche at 1 site in Italy.
Trial summary
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Lung Cancer, Renal Cell Carcinoma
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2019to 1 Jan 2022
- 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 referring to the Oncology and Hematology Clinics of the Azienda Ospedaliero- Universitaria Ospedali Riuniti di Ancona (Italy) may be enrolled.
Who may be able to join
- Adult patients above 18 years of age;
- Cyto-histological diagnosis of one of the following cancers:
- advanced melanoma;
- metastatic or locally advanced non-small cell lung cancer;
- advanced renal cell carcinoma;
- metastatic or locally advanced urotelial carcinoma;
Show all 15Show fewer
- squamous cell carcinoma of the head and neck;
- Hodgkin lymphoma;
- Merkel-cell carcinoma;
- New prescription of one of the following PD-1/PD-L1 inhibitors:
- nivolumab
- pembrolizumab
- atezolizumab
- avelumab
- durvalumab alone or in combination therapy, following the indications of the Italian regulatory agency (AIFA).
Who cannot join
- Patients that refuse and/or are not able to sign the Informed Consent;
- Parents/guardians or subjects who, in the opinion of the Investigator, may be noncompliant with study schedules or procedures;
- No contraindications to the treatment with PD-1/PD-L1 antibodies, following the indications of the Italian regulatory agency (AIFA).
- Subjects that do not meet all of the enrollment criteria may not be enrolled.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Università Politecnica delle Marche
Ancona, AN, 60020
Armando Gabrielli, MD, professor, 0712206104 ext. 0039, a.gabrielli@staff.univpm.it
Giovanni Pomponio, MD, 0715964205 ext. 0039, pomponio@univpm.it
About this study
Official title: Incidence, Clinical Management and Molecular Factors Associated With the Development of Immune-related Adverse Events in Cancer Patients Receiving PD-1 and PD-L1 Inhibitors: a Prospective Observational Study
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines. Durable responses and prolongation of survival with these agents come at the price of the development of immune related adverse events (irAEs). Innovative tools are required in order to manage irAEs and to prevent their potential relapse, with the goal to improve the outcome of patients. In this regard, the Investigators aim to develop a multidisciplinary clinical pathway for cancer patients that are treated with immune checkpoint inhibitors.
Read the detailed description
Recent evidences in immuno-oncology showed an important role of the immune system in tumor control. In fact, immune response, both innate and adaptive one, is the first defensive mechanism against cancer. However, several tumors, during their progression, develop an immune-tolerance characterized by the activation of immune inhibitory pathways including PD-1 and PD-L1.
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti-PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines.
Currently, the aforementioned agents are approved for the treatment of advanced malignant melanoma; non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) and the number of treatment indications for immune checkpoint inhibitors is expanding. Durable responses and prolongation of survival with these agents come at the price of the development of immune-related adverse events (irAEs).
Immune-related adverse events are due to the loss of immune-tolerance towards structures of the self, with the induction of chronic inflammation with an autoimmune mechanism that can involve numerous organs and systems. The most frequent irAEs reported in clinical trials are represented by skin toxicity, gastrointestinal toxicity, endocrine toxicity, pulmonary toxicity, and others such as polymyalgia rheumatica, polyarthritis, myositis, nephritis, polyradiculoneuritis, encephalitis and myocarditis.
The irAEs reported in clinical trials with nivolumab amount to a maximum of 85% considering all grade of toxicities, while approximately 75% of patients treated with pembrolizumab presented irAEs. Grade 3/4 irAEs were reported in 10% of patients treated with anti-PD-1. With atezolizumab fewer patients had treatment-related grade 3 or 4 adverse events (15%).
In most cases, irAEs occur within some weeks after starting of immunotherapy; however these toxicities have been reported later and also years after treatment discontinuation. The development of irAEs is associated with significant morbidity and mortality in cancer patients treated with immune checkpoint inhibitors, and therefore they may significantly affect the quality of life, even in patients achieve the control of neoplastic disease.
The overseeing, early diagnosis and clinical management of immune checkpoint inhibitors' toxicities in the clinical setting are, currently, not standardized.
Innovative tools are required in order to manage irAEs and to prevent their potential relapse, with the goal to improve the outcome and quality of life of these patients.
In this regard, the Investigators also aim to evaluate a model of multidisciplinary clinical pathway for cancer patients that are treated with immune checkpoint inhibitors in order to improve their management and also ameliorate the quality of life of patients that develop irAEs.
- Conditions
- Cancer, Lung Cancer, Renal Cell Carcinoma, Melanoma
- Keywords
- cancer, immune checkpoint inhibitors, immune related adverse events, nivolumab, pembrolizumab, avelumab, durvalumab, atezolizumab
- Medical subject headings
- Neoplasms, Lung Neoplasms, Carcinoma, Renal Cell, Melanoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of irAEs
To determine the incidence and the characteristics of irAEs in a real-world setting
Measured: 24 months
Risk factors for irAEs
To determine the risk factors for the development of irAEs
Measured: 24 months
Impact of irAEs
To determine the impact of irAEs on patients' prognosis
Measured: 24 months
Therapies of irAEs
To determine the effect of immunosuppressive therapies on tumor progression and patient's prognosis
Measured: 24 months
Secondary outcomes (4)
Clinical care pathway
To set up an integrated clinical care pathway for cancer patients that developed an irAE following immune checkpoint inhibitor administration
Measured: 24 months
Quality of life
The quality of life will be measured by means of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). It is composed by five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Measured: 24 months
Biomarkers
To evaluate potential biomarkers that may predict the development of irAEs and/or the response to treatment in biological samples from cancer patients treated with immune checkpoint inhibitors
Measured: 24 months
Exploratory analyses
To get better insights on the biological basis of irAEs the response to treatment in biological samples from cancer patients treated with immune checkpoint inhibitors
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start1 Jan 2019
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Jan 2022 (estimated)
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 CancerStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Politecnica delle Marche
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Armando Gabrielli, Università Politecnica delle Marche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04268368
- Sponsor's protocol ID
- ICI-DISCOVER
- Acronym
- ICI-DISCOVER
- Status last verified
- Feb 2020
- First submitted
- 10 Feb 2020
- Last updated
- 17 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
PubMed 29442540
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incidence, Clinical Management and Molecular Factors Associated With the Development of Immune-related Adverse Events in Cancer Patients Receiving PD-1 and PD-L1 Inhibitors: a Prospective Observational Study
- ClinicalTrials.gov ID
- NCT04268368
- Acronym / sponsor ID
- ICI-DISCOVER / ICI-DISCOVER
- Conditions
- Cancer, Lung Cancer, Renal Cell Carcinoma, Melanoma
- Keywords
- cancer, immune checkpoint inhibitors, immune related adverse events, nivolumab, pembrolizumab, avelumab, durvalumab, atezolizumab
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Università Politecnica delle MarcheUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 13 Feb 2020 (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.
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines. Durable responses and prolongation of survival with these agents come at the price of the development of immune related adverse events (irAEs). Innovative tools are required in order to manage irAEs and to prevent their potential relapse, with the goal to improve the outcome of patients. In this regard, the Investigators aim to develop a multidisciplinary clinical pathway for cancer patients that are treated with immune checkpoint inhibitors.
Detailed description
Recent evidences in immuno-oncology showed an important role of the immune system in tumor control. In fact, immune response, both innate and adaptive one, is the first defensive mechanism against cancer. However, several tumors, during their progression, develop an immune-tolerance characterized by the activation of immune inhibitory pathways including PD-1 and PD-L1.
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti-PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines.
Currently, the aforementioned agents are approved for the treatment of advanced malignant melanoma; non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) and the number of treatment indications for immune checkpoint inhibitors is expanding. Durable responses and prolongation of survival with these agents come at the price of the development of immune-related adverse events (irAEs).
Immune-related adverse events are due to the loss of immune-tolerance towards structures of the self, with the induction of chronic inflammation with an autoimmune mechanism that can involve numerous organs and systems. The most frequent irAEs reported in clinical trials are represented by skin toxicity, gastrointestinal toxicity, endocrine toxicity, pulmonary toxicity, and others such as polymyalgia rheumatica, polyarthritis, myositis, nephritis, polyradiculoneuritis, encephalitis and myocarditis.
The irAEs reported in clinical trials with nivolumab amount to a maximum of 85% considering all grade of toxicities, while approximately 75% of patients treated with pembrolizumab presented irAEs. Grade 3/4 irAEs were reported in 10% of patients treated with anti-PD-1. With atezolizumab fewer patients had treatment-related grade 3 or 4 adverse events (15%).
In most cases, irAEs occur within some weeks after starting of immunotherapy; however these toxicities have been reported later and also years after treatment discontinuation. The development of irAEs is associated with significant morbidity and mortality in cancer patients treated with immune checkpoint inhibitors, and therefore they may significantly affect the quality of life, even in patients achieve the control of neoplastic disease.
The overseeing, early diagnosis and clinical management of immune checkpoint inhibitors' toxicities in the clinical setting are, currently, not standardized.
Innovative tools are required in order to manage irAEs and to prevent their potential relapse, with the goal to improve the outcome and quality of life of these patients.
In this regard, the Investigators also aim to evaluate a model of multidisciplinary clinical pathway for cancer patients that are treated with immune checkpoint inhibitors in order to improve their management and also ameliorate the quality of life of patients that develop irAEs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients referring to the Oncology and Hematology Clinics of the Azienda Ospedaliero- Universitaria Ospedali Riuniti di Ancona (Italy) may be enrolled.
Key inclusion criteria (15 listed)
- Adult patients above 18 years of age;
- Cyto-histological diagnosis of one of the following cancers:
- New prescription of one of the following PD-1/PD-L1 inhibitors:
Key exclusion criteria (4 listed)
- Patients that refuse and/or are not able to sign the Informed Consent;
- Parents/guardians or subjects who, in the opinion of the Investigator, may be noncompliant with study schedules or procedures;
- No contraindications to the treatment with PD-1/PD-L1 antibodies, following the indications of the Italian regulatory agency (AIFA).
- Subjects that do not meet all of the enrollment criteria may not be enrolled.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Incidence of irAEs
Time frame: 24 months
To determine the incidence and the characteristics of irAEs in a real-world setting
Risk factors for irAEs
Time frame: 24 months
To determine the risk factors for the development of irAEs
Impact of irAEs
Time frame: 24 months
To determine the impact of irAEs on patients' prognosis
Therapies of irAEs
Time frame: 24 months
To determine the effect of immunosuppressive therapies on tumor progression and patient's prognosis
4 secondary outcomes
Clinical care pathway
Time frame: 24 months
Quality of life
Time frame: 24 months
Biomarkers
Time frame: 24 months
Exploratory analyses
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Background: PubMed 29442540Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
- Individual participant dataSharing planned: Undecided
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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.
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 Cancer and Lung Cancer, run by Università Politecnica delle Marche at 1 site in Italy.
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 15 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 17 Feb 2020. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Armando Gabrielli, M.D. (+390712206104, a.gabrielli@staff.univpm.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of irAEs (time frame: 24 months). The study lists 4 primary outcomes in all. 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 NCT04268368, 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 17 Feb 2020.