MelanomaG-DEFINERNCT04435964
Gender Difference in sidE eFfects of ImmuNotherapy: a Possible Clue to Optimize cancEr tReatment
An observational study of Melanoma and Lung Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
The study aim is to investigate the differences between sex and gender in the immune-related adverse events (irAEs) development associated with immune checkpoint inhibitors (ICI) treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Lung Cancer, Head and Neck Cancer
- What is being tested?
- Immunotherapy
- How many people
- 247 participants
- Where
- 1 siteItaly
- Study dates
- 25 Jun 2020to 28 Feb 2023
- 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: To allow for balanced sex groups, we will include patients according to the following stratification : ICI: 100 F/100 M; ICI+ CT/RT: 100 F/100 M. Due to the current ICI use in clinical practice we are expecting to mainly populate the ICI strata during the first recruitment period. As the recruitment progresses, the sample will be enriched of ICI+CT and ICI+RT treated patients, since combinations are expanding for many cancers such for instance melanoma, lung and head and neck
Who may be able to join
- Signed informed consent.
- Histologically confirmed diagnosis of one of the following cancers: melanoma, lung, head and neck, urogenital, breast cancer. In addition, other solid tumors characterized by the presence of microsatellite instability (MSI-high), treated with immunocheckpoint inhibitors (ICI) irrespective of treatment schedule. It is possible to include patients treated with Immunotherapy in a compassionate use setting.
- Any disease stage.
- Patients eligible for immune checkpoint inhibitors (ICI)-containing regimens: ICI single agent; Combination of ICIs; ICI-chemotherapy combination; ICI-radiotherapy combination.
- Any treatment setting (neoadjuvant, adjuvant, advanced disease, maintenance).
- Patient age ≥18 years
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- ECOG Performance Status of 0-2.
- Adequate bone marrow, liver and renal function.
- Life expectancy of at least 12 weeks.
Who cannot join
- Patients not eligible for ICI-containing regimens.
Trial locations and contacts
1 site in 1 country.
About this study
The study aim is to investigate the differences between sex and gender in the immune-related adverse events (irAEs) development associated with immune checkpoint inhibitors (ICI) treatment. The study will be a multicenter prospective observational study focusing on biological differences between females and males, possibly affecting discrepant irAEs incidence.
Read the detailed description
The study aim is to investigate the differences between sex and gender in the immune-related adverse events (irAEs) development associated with immune checkpoint inhibitors (ICI) treatment.
In common feeling, sex and gender represent the same concept, that is the traditional division of individuals into females (F) and males (M) defined by differential organization of chromosomes, reproductive organs, and sex steroid levels. However, if going beyond these aspects, which characterize "sex", it can be observed how the differences between people are also characterized by behaviors and relationships that are the product of the culture and sociality typical of human beings. This is what is called "gender", i.e. the process of social and cultural construction that determines the behaviors that give life to the status of an individual. Gender is therefore learned and not innate. Sex and gender do not constitute two opposing but interdependent dimensions: the process of determining gender identity is triggered on biological characters. The relationship between sex and gender varies according to geographical areas, historical periods and cultures.
Sex influences the adaptive immunity, and may influence irAEs types, frequency and severity. Together with genetic and biological differences, the roots of irAEs inequalities between F and M could be linked to psycho-social and behavioral determinants. IrAEs usually develop within the first few weeks to 6 months after treatment initiation; however, they can also present after cessation of ICI therapy. Most studies indicate that prolonged treatment does not result in an increased cumulative incidence of irAEs. Accumulating evidences support the existence of sex-driven differences in immune responses as potential factors contributing to disease outcome and response to therapy. Increasing use of ICI is associated with immune-related adverse events caused by non-specific activation of the immune system.
The investigators will conduct a multicenter prospective observational study investigating sex differences in irAEs in relation to clinical factors and genetic, immunological and hormonal profiles. By focusing on biological F/M differences possibly affecting discrepant irAEs incidence, sex inequality will be explicitly addressed and complemented by the exploration of association between gender dimension and irAEs development. Exploring the irAEs occurrence in a "real world" (outside RCT) context will be more easily translated in a ready-to-use personalized approach to irAEs timely diagnosis and treatment.
- Conditions
- Melanoma, Lung Cancer, Head and Neck Cancer, Urogenital Neoplasms, Breast Cancer
- Being tested
- Immunotherapy
- Medical subject headings
- Melanoma, Lung Neoplasms, Head and Neck Neoplasms, Urogenital Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImmunotherapyDrug
Also called Chemotherapy, Radiotherapy
Patients treated as per clinical prescription with immunocheckpoint inhibitors (ICI) irrespective of treatment schedule, either as single agent or in combination with chemotherapy and/or radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Overall series | Patients treated with immunocheckpoint inhibitors (ICI) irrespective of treatment schedule. No limitations to previous lines of treatment. ICI therapy may be either as single agent or in combination. Concomitant chemotherapy (CT) and radiotherapy (RT) is allowed. Receives: Drug: Immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune-related severe (G≥ 2) adverse events (irAEs)
The incidence of first severe (G≥ 2) irAEs of any type will be estimated in females and males
Measured: 1 year
Secondary outcomes (1)
Immune-related adverse events (irAEs)
The incidence of irAEs of any type and any grade will be estimated in females and males
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2020
- Study start25 Jun 2020
- Primary completion28 Feb 2023
- Study completion28 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe 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
- Prospective
- Enrolment
- 247 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital, St Vincent's University Hospital, Ireland, Oslo University Hospital
- Responsible party
- Sponsor
- Investigators
- Rosalba Miceli, PhD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04435964
- Sponsor's protocol ID
- INT156-19
- Acronym
- G-DEFINER
- Status last verified
- Sep 2021
- First submitted
- 11 Jun 2020
- Last updated
- 24 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gender Difference in sidE eFfects of ImmuNotherapy: a Possible Clue to Optimize cancEr tReatment
- ClinicalTrials.gov ID
- NCT04435964
- Acronym / sponsor ID
- G-DEFINER / INT156-19
- Conditions
- Melanoma, Lung Cancer, Head and Neck Cancer, Urogenital Neoplasms, Breast Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 247 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Collaborators
- Karolinska University Hospital, St Vincent's University Hospital, Ireland, Oslo University Hospital
- Study start
- 25 Jun 2020 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 17 Jun 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 study aim is to investigate the differences between sex and gender in the immune-related adverse events (irAEs) development associated with immune checkpoint inhibitors (ICI) treatment. The study will be a multicenter prospective observational study focusing on biological differences between females and males, possibly affecting discrepant irAEs incidence.
Detailed description
The study aim is to investigate the differences between sex and gender in the immune-related adverse events (irAEs) development associated with immune checkpoint inhibitors (ICI) treatment.
In common feeling, sex and gender represent the same concept, that is the traditional division of individuals into females (F) and males (M) defined by differential organization of chromosomes, reproductive organs, and sex steroid levels. However, if going beyond these aspects, which characterize "sex", it can be observed how the differences between people are also characterized by behaviors and relationships that are the product of the culture and sociality typical of human beings. This is what is called "gender", i.e. the process of social and cultural construction that determines the behaviors that give life to the status of an individual. Gender is therefore learned and not innate. Sex and gender do not constitute two opposing but interdependent dimensions: the process of determining gender identity is triggered on biological characters. The relationship between sex and gender varies according to geographical areas, historical periods and cultures.
Sex influences the adaptive immunity, and may influence irAEs types, frequency and severity. Together with genetic and biological differences, the roots of irAEs inequalities between F and M could be linked to psycho-social and behavioral determinants. IrAEs usually develop within the first few weeks to 6 months after treatment initiation; however, they can also present after cessation of ICI therapy. Most studies indicate that prolonged treatment does not result in an increased cumulative incidence of irAEs. Accumulating evidences support the existence of sex-driven differences in immune responses as potential factors contributing to disease outcome and response to therapy. Increasing use of ICI is associated with immune-related adverse events caused by non-specific activation of the immune system.
The investigators will conduct a multicenter prospective observational study investigating sex differences in irAEs in relation to clinical factors and genetic, immunological and hormonal profiles. By focusing on biological F/M differences possibly affecting discrepant irAEs incidence, sex inequality will be explicitly addressed and complemented by the exploration of association between gender dimension and irAEs development. Exploring the irAEs occurrence in a "real world" (outside RCT) context will be more easily translated in a ready-to-use personalized approach to irAEs timely diagnosis and treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Overall series | – | Drug: ImmunotherapyPatients treated with immunocheckpoint inhibitors (ICI) irrespective of treatment schedule. No limitations to previous lines of treatment. ICI therapy may be either as single agent or in combination. Concomitant chemotherapy (CT) and radiotherapy (RT) is allowed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- To allow for balanced sex groups, we will include patients according to the following stratification : ICI: 100 F/100 M; ICI+ CT/RT: 100 F/100 M. Due to the current ICI use in clinical practice we are expecting to mainly populate the ICI strata during the first recruitment period. As the recruitment progresses, the sample will be enriched of ICI+CT and ICI+RT treated patients, since combinations are expanding for many cancers such for instance melanoma, lung and head and neck
Key inclusion criteria (9 listed)
- Signed informed consent.
- Histologically confirmed diagnosis of one of the following cancers: melanoma, lung, head and neck, urogenital, breast cancer. In addition, other solid tumors characterized by the presence of microsatellite instability (MSI-high), treated with immunocheckpoint inhibitors (ICI) irrespective of treatment schedule. It is possible to include patients treated with Immunotherapy in a compassionate use setting.
- Any disease stage.
- Patients eligible for immune checkpoint inhibitors (ICI)-containing regimens: ICI single agent; Combination of ICIs; ICI-chemotherapy combination; ICI-radiotherapy combination.
- Any treatment setting (neoadjuvant, adjuvant, advanced disease, maintenance).
Key exclusion criteria (1 listed)
- Patients not eligible for ICI-containing regimens.
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 |
|---|---|---|
| ImmunotherapyAlso: Chemotherapy, RadiotherapyPatients treated as per clinical prescription with immunocheckpoint inhibitors (ICI) irrespective of treatment schedule, either as single agent or in combination with chemotherapy and/or radiotherapy | Drug | Overall series |
Primary outcome
Immune-related severe (G≥ 2) adverse events (irAEs)
Time frame: 1 year
The incidence of first severe (G≥ 2) irAEs of any type will be estimated in females and males
1 secondary outcome
Immune-related adverse events (irAEs)
Time frame: 1 year
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 Mar 2023.
- 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.
Rosalba Miceli, PhD principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
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 Melanoma and Lung Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano 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 9 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 24 Mar 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 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?
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?
Immune-related severe (G≥ 2) adverse events (irAEs) (time frame: 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 24 Mar 2023.