Lung Cancer, Nonsmall CellPhase 1/2ICEMELTNCT04631731
Risk Factors of Immune-ChEckpoint Inhibitors MEdiated Liver, Gastrointestinal, Endocrine and Skin Toxicity
A Phase 1/2 study testing Blood screening and Tissue screening in people with Lung Cancer, Nonsmall Cell and Renal Cell Carcinoma, run by Western Sydney Local Health District at 2 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lung Cancer, Nonsmall Cell, Renal Cell Carcinoma, Melanoma
- What is being tested?
- Blood screening and Tissue screening
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 2 sitesAustralia
- Study dates
- 15 Dec 2020to 10 Dec 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country.
Australia2 sites, 2 recruiting
- Recruiting
Westmead Hospital
Sydney, New South Wales, 2145
Bo Gao, Dr, Bo.Gao@health.nsw.gov.au
Adnan Nagrial, A/Professor, Adnan.Nagrial@health.nsw.gov.au
- Recruiting
Blacktown Mt Druitt Hospital
Sydney, New South Wales, 2148
Bo Gao, Dr, Bo.Gao@health.nsw.gov.au
Matteo Carlino, A/Professor, Matteo.Carlino@health.nsw.gov.au
About this study
"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.
Read the 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.
- Conditions
- Lung Cancer, Nonsmall Cell, Renal Cell Carcinoma, Melanoma, Gastric Cancer, Hepatocellular Carcinoma, Endometrial Cancer
- Being tested
- Blood screening, Tissue screening
- Keywords
- Immune-checkpoint inhibitors, Immunotherapy, Nivolumab, Iplimumab, Pembrolizumab, Atezolizumab, Durvalumab, CTLA-4, PD-1, PD-L1, Tislelizumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Melanoma, Stomach Neoplasms, Carcinoma, Hepatocellular, Endometrial Neoplasms, Mesothelioma, Diabetes Mellitus, Insulin-Dependent, 12
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Single agent PD-1/L1 inhibitor | Experimental | Not described Receives: Diagnostic Test: Blood screening; Diagnostic Test: Tissue screening |
| PD-1/L1 inhibitor + CTLA-4 inhibitor | Experimental | Not described Receives: Diagnostic Test: Blood screening; Diagnostic Test: Tissue screening |
| Platinum-based chemotherapy + PD-1/L1 inhibitor | Experimental | Not described Receives: Diagnostic Test: Blood screening; Diagnostic Test: Tissue screening |
| PD-1/L1 inhibitor + tyrosine kinase inhibitor | Experimental | Not described Receives: Diagnostic Test: Blood screening; Diagnostic Test: Tissue screening |
| PD-1/L1 inhibitor + VEGF inhibitor | Experimental | Not described Receives: Diagnostic Test: Blood screening; Diagnostic Test: Tissue screening |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differentially expressed genes in circulating immune cells between patients with and without irAEs.
This objective will be achieved through single-cell sequencing.
Measured: 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.
Measured: Week 0-48
Secondary outcomes (1)
Association of pre-treatment BMI, neutrophil-to-lymphocyte ratio and other clinical parameters with irAEs.
Measured: Week 0-48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start15 Dec 2020
- Primary completion10 Dec 2024 (estimated)
- Study completion10 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lung Cancer, Nonsmall CellStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western Sydney Local Health District
- Sponsor type
- University, hospital or other
- Collaborators
- University of Western Sydney, Bristol-Myers Squibb
- Responsible party
- Principal investigator, Golo Ahlenstiel, Western Sydney Local Health District
- Investigators
- Golo Ahlenstiel, Professor, Principal investigator, Western Sydney Local Health District
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04631731
- Sponsor's protocol ID
- 2020/PID02542
- Acronym
- ICEMELT
- Status last verified
- May 2023
- First submitted
- 10 Nov 2020
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 32378480Shek 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.
PubMed 33818870Shek 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.
PubMed 34503155Shek 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.
PubMed 37104017
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk Factors of Immune-ChEckpoint Inhibitors MEdiated Liver, Gastrointestinal, Endocrine and Skin Toxicity
- ClinicalTrials.gov ID
- NCT04631731
- Acronym / sponsor ID
- ICEMELT / 2020/PID02542
- Conditions
- Lung Cancer, Nonsmall Cell, Renal Cell Carcinoma, Melanoma, Gastric Cancer, Hepatocellular Carcinoma, Endometrial Cancer
- Keywords
- Immune-checkpoint inhibitors, Immunotherapy, Nivolumab, Iplimumab, Pembrolizumab, Atezolizumab, Durvalumab, CTLA-4
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Western Sydney Local Health DistrictUniversity, hospital or other
- Collaborators
- University of Western Sydney, Bristol-Myers Squibb
- Study start
- 15 Dec 2020 (actual)
- Primary completion
- 10 Dec 2024 (estimated)
- Study completion
- 10 Dec 2025 (estimated)
- First posted
- 17 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
"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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Single agent PD-1/L1 inhibitor | Experimental | Diagnostic Test: Blood screening, Diagnostic Test: Tissue screening |
| PD-1/L1 inhibitor + CTLA-4 inhibitor | Experimental | Diagnostic Test: Blood screening, Diagnostic Test: Tissue screening |
| Platinum-based chemotherapy + PD-1/L1 inhibitor | Experimental | Diagnostic Test: Blood screening, Diagnostic Test: Tissue screening |
| PD-1/L1 inhibitor + tyrosine kinase inhibitor | Experimental | Diagnostic Test: Blood screening, Diagnostic Test: Tissue screening |
| PD-1/L1 inhibitor + VEGF inhibitor | Experimental | Diagnostic Test: Blood screening, Diagnostic Test: Tissue screening |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood screeningBlood 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 | PD-1/L1 inhibitor + CTLA-4 inhibitor, PD-1/L1 inhibitor + VEGF inhibitor, PD-1/L1 inhibitor + tyrosine kinase inhibitor, Platinum-based chemotherapy + PD-1/L1 inhibitor, Single agent PD-1/L1 inhibitor |
| Tissue screeningArchival 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. | Diagnostic test | PD-1/L1 inhibitor + CTLA-4 inhibitor, PD-1/L1 inhibitor + VEGF inhibitor, PD-1/L1 inhibitor + tyrosine kinase inhibitor, Platinum-based chemotherapy + PD-1/L1 inhibitor, Single agent PD-1/L1 inhibitor |
Primary outcome
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.
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.
1 secondary outcome
Association of pre-treatment BMI, neutrophil-to-lymphocyte ratio and other clinical parameters with irAEs.
Time frame: Week 0-48
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
- Background: PubMed 32378480Shek 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.
- Background: PubMed 33818870Shek 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.
- Background: PubMed 34503155Shek 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.
- Results publication: PubMed 37104017Shek 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Golo Ahlenstiel, Professor principal investigator
Western Sydney Local Health District
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Blood screening and Tissue screening in people with Lung Cancer, Nonsmall Cell and Renal Cell Carcinoma, run by Western Sydney Local Health District at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dmitrii Shek, Dr (+61 412 035 533, Dmitri.Shek@health.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differentially expressed genes in circulating immune cells between patients with and without irAEs. (time frame: Week 0-48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04631731, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2023.