LATe TreatmENT Related Toxicity in Melanoma (LATENT)

Melanoma Clinical Trial

— LATENT  

Official title:

LATe TreatmENT Related Toxicity in Melanoma (LATENT)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06414343
• Other study ID #: CCR6009
• Status: Not yet recruiting
• Start date: May 2024
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Royal Marsden NHS Foundation Trust
• Contact: Arjun Modi
• Phone: 020 7352 8171
• Email: arjun.modi[@]rmh.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recent improvements in advanced melanoma treatment with immunotherapy have dramatically improved patient survival. Longer survival however has come at a cost of toxicity. Short term side effects can occur in >50% of patients undergoing immunotherapy treatment; however, many long-term survivors are also living with serious consequences of these treatments which may be under reported in literature.

Data regarding long term toxicities, from these treatments is lacking and an area of important unmet clinical need. Therefore, in collaboration with the Clatterbridge and Christie's teams, the investigators propose to retrospectively analyse the nature, incidence, frequency, and severity of immune related toxicities in around 400 patients who received immunotherapy for advanced melanoma with ongoing durable responses to treatment of at least 3 years.

The investigators will set up a collective anonymized database and record this information through review of electronic medical records of patients that meet the eligibility criteria. The investigators will also review the patterns of use of long-term immunosuppression and assess the need for specialist referrals for managing late side effects.

The investigators hope that this data will help us address gaps in the management of long-term survivors by identifying areas of need and establishing a coordinated evidence based multidisciplinary service to provide personalised, risk stratified long term follow up.

Description:

LATENT will be a retrospective non-interventional analysis of pre-existing data from patient medical records and, therefore patients will not be required to participate in any risky procedures, treatments or hospital visits. The study will therefore not require explicit informed consent from eligible participants.

A potential ethical issue could arise around explicit consent of patients for collection and publication of their data. The investigators aim to circumvent this by only using data that has already been recorded from direct patient care.

The investigators will pseudo-anonymise personal data and mitigate risk of identification through:

1. Direct health care providers screening for eligible patients from clinic records based on clear inclusion and exclusion criteria

2. Allocation of de-identified serial numbers for patients on the database used to collect and record relevant data

3. Exportation and storage of de-identified data from all sites on a common trusted research environment (TRE) 'BRIDGE' for blinded analysis by the Research team

4. Reporting of anonymised/de-identified data only, for publication

In addition, the investigators aim to reduce selection bias by eliminating the need for explicit consent as unwell patients with greater clinical needs may be unable to consent and would not be included in the study, thereby only selecting for well patients and potentially underrepresenting a vital group of patients, compromising the scientific validity of the study.

As this is a multicentre study, de-identified, anonymised data from all centres will be exported and stored in a single secure password protected TRE for analysis. The main centre in charge of maintaining and analysing the database, with appropriate data sharing agreements with individual sites, will be The Royal Marsden team.

The investigators do not anticipate any legal issues arising from this study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological diagnosis of melanoma

• Age 18 years or older

• Treated between January 2005- December 2020 with immune checkpoint inhibitor therapy including either Pembrolizumab, Nivolumab, Ipilimumab or combinations, for advanced melanoma (unresectable stage III or stage IV)

• Ongoing response to therapy of at least 3 years duration at point of study entry

Exclusion Criteria:

• Diagnoses of other concurrent malignancies needing active treatment

• Received Immune checkpoint inhibitors for non-metastatic melanoma or in the adjuvant setting only.

• Received other treatments including targeted therapy as the most recent line of treatment or following immunotherapy.

• Progression of disease on or following immunotherapy

Related Conditions & MeSH terms

• Melanoma

Intervention

Other:
• Observational - no intervention
Observational - no intervention

Locations

Country	Name	City	State
United Kingdom	Royal Marsden NHS Foundation Trust	Chelsea	London

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To describe patterns of a range of medical late toxicities following immunotherapy treatment for advanced melanoma patients	• Descriptive analysis of proportion of patients (%) developing immune related adverse events in those with advanced melanoma with ongoing response of at least 3 years following treatment with immune checkpoint inhibitors. Description of severity of each type of toxicity and adverse events experienced in the overall population measured as Grade 1-5 as per Common Terminology Criteria for Adverse Events (CTCAE v5.0).	12 months
Secondary	Exploration of differences in proportions of patients	• Exploration of differences in proportions of patients developing different types and severities of late toxicities according to treatment type (single vs doublet immunotherapy), disease (stage, mutational status) and patient characteristics (eg; age, gender, smoking status, etc) using univariate and multivariate analyses.	12 months
Secondary	Time to occurrence of irAEs	• Time to occurrence of irAEs using Kaplan-Meier survival analysis measured in years and months.	12 months
Secondary	Descriptive analyses of the frequency of use of immunosuppressive agents	• Descriptive analyses of the frequency of use of immunosuppressive agents used (%) for treating late immune toxicities for each type of agent, toxicity and duration of immunosuppressive treatment.	12 months