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Risk Factors of Immune-ChEckpoint Inhibitors MEdiated Liver, Gastrointestinal, Endocrine and Skin Toxicity
"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.
Study 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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2020-12-15
Primary completion: 2024-12-10
Study completion finish: 2025-12-10
Study type
DIAGNOSTIC
Phase
PHASE1
PHASE2
Trial ID
NCT04631731
Intervention or treatment
DIAGNOSTIC_TEST: Blood screening
DIAGNOSTIC_TEST: Tissue screening
Conditions
- • Gastric Cancer
- • Endometrial Cancer
- • Lung Cancer, Nonsmall Cell
- • Renal Cell Carcinoma
- • Melanoma
- • Hepatocellular Carcinoma
- • Mesothelioma
Find a site
Closest Location:
Westmead Hospital
Research sites nearby
Select from list below to view details:
Westmead Hospital
Sydney, New South Wales, Australia
Blacktown Mt Druitt Hospital
Sydney, New South Wales, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Single agent PD-1/L1 inhibitor
| DIAGNOSTIC_TEST: Blood screening
|
EXPERIMENTAL: PD-1/L1 inhibitor + CTLA-4 inhibitor
| DIAGNOSTIC_TEST: Blood screening
|
EXPERIMENTAL: Platinum-based chemotherapy + PD-1/L1 inhibitor
| DIAGNOSTIC_TEST: Blood screening
|
EXPERIMENTAL: PD-1/L1 inhibitor + tyrosine kinase inhibitor
| DIAGNOSTIC_TEST: Blood screening
|
EXPERIMENTAL: PD-1/L1 inhibitor + VEGF inhibitor
| DIAGNOSTIC_TEST: Blood screening
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| Differentially expressed genes in circulating immune cells between patients with and without irAEs. | This objective will be achieved through single-cell sequencing. | Week 0-48 |
| Expression of TIM-3, LAG3, VISTA and other inhibitory checkpoint molecules on tumour-infiltrating T cells. | In order to ascertain this result, our objective is to utilize spatial transcriptomics and mass spectrometry. | Week 0-48 |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Association of pre-treatment BMI, neutrophil-to-lymphocyte ratio and other clinical parameters with irAEs. | Not Specified | Week 0-48 |
Frequently Asked Questions
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