NCT04631731

Brief Summary

"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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2020

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 10, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 17, 2020

Completed
28 days until next milestone

Study Start

First participant enrolled

December 15, 2020

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 10, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 10, 2025

Completed
Last Updated

June 1, 2023

Status Verified

May 1, 2023

Enrollment Period

4 years

First QC Date

November 10, 2020

Last Update Submit

May 28, 2023

Conditions

Keywords

Immune-checkpoint inhibitorsImmunotherapyNivolumabIplimumabPembrolizumabAtezolizumabDurvalumabCTLA-4PD-1PD-L1Tislelizumab

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (1)

  • Association of pre-treatment BMI, neutrophil-to-lymphocyte ratio and other clinical parameters with irAEs.

    Week 0-48

Study Arms (5)

Single agent PD-1/L1 inhibitor

EXPERIMENTAL
Diagnostic Test: Blood screeningDiagnostic Test: Tissue screening

PD-1/L1 inhibitor + CTLA-4 inhibitor

EXPERIMENTAL
Diagnostic Test: Blood screeningDiagnostic Test: Tissue screening

Platinum-based chemotherapy + PD-1/L1 inhibitor

EXPERIMENTAL
Diagnostic Test: Blood screeningDiagnostic Test: Tissue screening

PD-1/L1 inhibitor + tyrosine kinase inhibitor

EXPERIMENTAL
Diagnostic Test: Blood screeningDiagnostic Test: Tissue screening

PD-1/L1 inhibitor + VEGF inhibitor

EXPERIMENTAL
Diagnostic Test: Blood screeningDiagnostic Test: Tissue screening

Interventions

Blood screeningDIAGNOSTIC_TEST

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.

PD-1/L1 inhibitor + CTLA-4 inhibitorPD-1/L1 inhibitor + VEGF inhibitorPD-1/L1 inhibitor + tyrosine kinase inhibitorPlatinum-based chemotherapy + PD-1/L1 inhibitorSingle agent PD-1/L1 inhibitor
Tissue screeningDIAGNOSTIC_TEST

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.

PD-1/L1 inhibitor + CTLA-4 inhibitorPD-1/L1 inhibitor + VEGF inhibitorPD-1/L1 inhibitor + tyrosine kinase inhibitorPlatinum-based chemotherapy + PD-1/L1 inhibitorSingle agent PD-1/L1 inhibitor

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Westmead Hospital

Sydney, New South Wales, 2145, Australia

RECRUITING

Blacktown Mt Druitt Hospital

Sydney, New South Wales, 2148, Australia

RECRUITING

Related Publications (4)

  • Shek D, Read SA, Akhuba L, Qiao L, Gao B, Nagrial A, Carlino MS, Ahlenstiel G. Non-coding RNA and immune-checkpoint inhibitors: friends or foes? Immunotherapy. 2020 May;12(7):513-529. doi: 10.2217/imt-2019-0204. Epub 2020 May 7.

    PMID: 32378480BACKGROUND
  • Shek D, Read SA, Nagrial A, Carlino MS, Gao B, George J, Ahlenstiel G. Immune-Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Synopsis of Response Rates. Oncologist. 2021 Jul;26(7):e1216-e1225. doi: 10.1002/onco.13776. Epub 2021 Apr 21.

    PMID: 33818870BACKGROUND
  • Shek D, Akhuba L, Carlino MS, Nagrial A, Moujaber T, Read SA, Gao B, Ahlenstiel G. Immune-Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review of Clinical Outcomes. Cancers (Basel). 2021 Aug 27;13(17):4345. doi: 10.3390/cancers13174345.

    PMID: 34503155BACKGROUND
  • Shek D, Gloss B, Lai J, Ma L, Zhang HE, Carlino MS, Mahajan H, Nagrial A, Gao B, Read SA, Ahlenstiel G. Identification and Characterisation of Infiltrating Immune Cells in Malignant Pleural Mesothelioma Using Spatial Transcriptomics. Methods Protoc. 2023 Mar 28;6(2):35. doi: 10.3390/mps6020035.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungCarcinoma, Renal CellMelanomaStomach NeoplasmsCarcinoma, HepatocellularEndometrial NeoplasmsMesotheliomaDiabetes Mellitus, Insulin-Dependent, 12

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital DiseasesNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsSkin DiseasesSkin and Connective Tissue DiseasesGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesStomach DiseasesLiver NeoplasmsLiver DiseasesUterine NeoplasmsGenital Neoplasms, FemaleUterine DiseasesGenital Diseases, FemaleGenital DiseasesAdenomaNeoplasms, Mesothelial

Study Officials

  • Golo Ahlenstiel, Professor

    Western Sydney Local Health District

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

November 10, 2020

First Posted

November 17, 2020

Study Start

December 15, 2020

Primary Completion

December 10, 2024

Study Completion

December 10, 2025

Last Updated

June 1, 2023

Record last verified: 2023-05

Locations