Gender Difference in sidE eFfects of ImmuNotherapy: a Possible Clue to Optimize cancEr tReatment

NCT ID: NCT04435964

Last Updated: 2023-03-24

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 247 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-06-25
• Study Completion Date: 2023-02-28

Brief 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. 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.

Conditions

Melanoma; Lung Cancer; Head and Neck Cancer; Urogenital Neoplasms; Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Immunotherapy

Intervention Type: DRUG

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

Interventions

Immunotherapy

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

Intervention Type: DRUG

Other Intervention Names

Chemotherapy; Radiotherapy

Eligibility Criteria

Inclusion Criteria

• 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
• ECOG Performance Status of 0-2.
• Adequate bone marrow, liver and renal function.
• Life expectancy of at least 12 weeks.

Exclusion Criteria

• Patients not eligible for ICI-containing regimens.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

St Vincent's University Hospital, Ireland

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rosalba Miceli, PhD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Countries

Italy

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

INT156-19

Identifier Type: -

Identifier Source: org_study_id