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

May 28, 2023 updated by: Golo Ahlenstiel, Western Sydney Local Health District
"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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

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?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single agent PD-1/L1 inhibitor
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.
Experimental: PD-1/L1 inhibitor + CTLA-4 inhibitor
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.
Experimental: Platinum-based chemotherapy + PD-1/L1 inhibitor
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.
Experimental: PD-1/L1 inhibitor + tyrosine kinase inhibitor
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.
Experimental: PD-1/L1 inhibitor + VEGF inhibitor
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differentially expressed genes in circulating immune cells between patients with and without irAEs.
Time Frame: Week 0-48
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.
Time Frame: Week 0-48
In order to ascertain this result, our objective is to utilize spatial transcriptomics and mass spectrometry.
Week 0-48

Secondary Outcome Measures

Outcome Measure
Time Frame
Association of pre-treatment BMI, neutrophil-to-lymphocyte ratio and other clinical parameters with irAEs.
Time Frame: Week 0-48
Week 0-48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Western Sydney Local Health District

Collaborators

Bristol-Myers Squibb
University of Western Sydney

Investigators

  • Principal Investigator: Golo Ahlenstiel, Professor, Western Sydney Local Health District

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2020

Primary Completion (Estimated)

December 10, 2024

Study Completion (Estimated)

December 10, 2025

Study Registration Dates

First Submitted

November 10, 2020

First Submitted That Met QC Criteria

November 10, 2020

First Posted (Actual)

November 17, 2020

Study Record Updates

Last Update Posted (Actual)

June 1, 2023

Last Update Submitted That Met QC Criteria

May 28, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020/PID02542

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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