Risk Factors of Immune-ChEckpoint Inhibitors MEdiated Liver, Gastrointestinal, Endocrine and Skin Toxicity

Study Purpose

"Risk factors of Immune-ChEckpoint inhibitor MEdiated Liver, gastrointestinal, endocrine and skin Toxicity" (ICEMELT) study is a prospective multicenter cohort study, enrolling patients who are scheduled to receive

(1) single agent PD1/L1 inhibitor; (2) PD1/L1 inhibitor plus CTLA4 inhibitor; (3) platinum-based chemotherapy + PD1/L1 inhibitor; (4) PD1/L1 inhibitor and tyrosine kinase inhibitor and (5) PD1/L1 inhibitor and vascular endothelial growth factor (VEGF) inhibitor.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	N/A and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Able to comprehend the requirements and procedures for the study and to provide informed consent before entering the study.

- Solid malignant tumour (stage III-IV) - Treated with ICI-based therapeutic regimens.

Exclusion Criteria:

- Inability to give written informed consent.

- Patients with a cognitive impairment, an intellectual disability or a mental condition that will interfere with the patient's ability to understand the requirements of the study

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04631731
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Western Sydney Local Health District
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Golo Ahlenstiel, Professor
Principal Investigator Affiliation	Western Sydney Local Health District
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	Australia
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lung Cancer, Nonsmall Cell, Renal Cell Carcinoma, Melanoma, Gastric Cancer, Hepatocellular Carcinoma, Endometrial Cancer, Mesothelioma

Additional Details

This project is based on strong multidisciplinary collaboration between oncologists, gastroenterologists/hepatologists, immunologists and basic scientists affiliated with

(1) Western Sydney University, (2) University of Sydney, (3) Western Sydney Local Health District (4) New South Wales Health Pathology, (5) Westmead Institute for Medical Research.

Recruitment sites:

- Blacktown Mt Druitt Hospital.

- Westmead Hospital.

Research samples collection, processing and storage:

- Blacktown Clinical School, Western Sydney University.

- Westmead Institute for Medical Research, the University of Sydney.

- New South Wales Health Pathology.

Potential patients will be identified by study investigators at Oncology clinics. After informed consent, clinicopathological data including patients' demographics, past medical history, cancer staging, relevant anticancer treatment, response/progression and survival will be collected longitudinally. The following specimens will be collected from all participating patients at baseline (pre-treatment stage):

- Peripheral blood (3 x 10mL EDTA tubes) - FibroScan (CAP score for elucidating pre-existing liver fibrosis) - Formalin-Fixed Paraffin-Embedded (FFPE) samples (one block) from core biopsies which is a part of routine care for cancer patients.

The following specimens will be collected after IPI + NIVO therapeutic regimen will be commenced (week 6-9 after ICI-therapy commencement): • Peripheral blood (3 x 10mL EDTA tubes) Upon development of potential grade ≥2 irAEs, the following samples will be collected:

- Peripheral blood (3 x 10mL EDTA tubes) - FibroScan (for patients with hepatic irAEs) - Tissue samples (if biopsies are collected as per standard of care for patients with immune-mediated colitis who will be required to undergo colonoscopy) Peripheral blood samples from patients will be collected using 10ml EDTA vacutainer tubes (x3) and processed within 12 hours of collection by research staff at each site.

Plasma will be used for miRNA assay. PBMCs will be split into 5 cryotubes and used for flow cytometry and single-cell sequencing. Consent to the study will allow researchers to access the baseline archive diagnostic FFPE tissue samples. With implementing cutting-edge spatial analysis we aim to elucidate the impact of tumour-infiltrating immune microenvironment on clinical outcomes of ICI therapy. Fresh tissue samples obtained from patients with severe immune-mediated colitis will be processed to obtain total RNA and immune cells for sequencing and mass spectrometry (CyTOF). In addition, tissue samples will be analysed with in situ spatial profiling technologies to map multi-omic data on subcellular level and to determine its association with the clinical outcomes of cancer immunotherapy.

Arms & Interventions

Arms

Experimental: Single agent PD-1/L1 inhibitor

Experimental: PD-1/L1 inhibitor + CTLA-4 inhibitor

Experimental: Platinum-based chemotherapy + PD-1/L1 inhibitor

Experimental: PD-1/L1 inhibitor + tyrosine kinase inhibitor

Experimental: PD-1/L1 inhibitor + VEGF inhibitor

Interventions

Diagnostic Test: - Blood screening

Blood will be taken in order to elucidate transcriptomic and proteomic differences (1) pre- and post-ICI treatment commencement; (2) in patients with and without immune-related adverse events.

Diagnostic Test: - Tissue screening

Archival tumor tissue (FFPE) will be spatially analysed in order to define tissue heterogeneity in tumor samples regarding cancer immune cell transcriptional profiles and correlate it with the occurrence/development of immune-related adverse events.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Westmead Hospital, Sydney 2147714, New South Wales 2155400, Australia

Status

Recruiting

Address

Westmead Hospital

Sydney 2147714, New South Wales 2155400, 2145

Site Contact

Bo Gao, Dr

[email protected]

+61 412 035 533

Blacktown Mt Druitt Hospital, Sydney 2147714, New South Wales 2155400, Australia