MelanomaICI-PICKNCT05707286
Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
An observational study of Melanoma and Gastrointestinal Neoplasms, run by Indiana University at 1 site in United States.
Trial summary
This research aims to identify clinical strategies to manage adverse events during immune checkpoint inhibitor therapy by (1) determining the impact of checkpoint inhibitors on metabolism through major CYP enzymes and (2) identifying associations between pro-inflammatory cytokine concentrations and negative clinical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Gastrointestinal Neoplasms, Genitourinary Cancer
- How many people
- 98 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Sep 2023to 20 Jan 2025
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults diagnosed with solid cancers and initiating therapy with an immune checkpoint inhibitor
Who may be able to join
- ≥ 18 years old at the time of informed consent
- Diagnosed with non-small cell lung cancer (NSCLC) OR melanoma AND initiating therapy with single agent or combination therapy that includes an immune checkpoint inhibitor, (e.g., atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab)
- Ability to provide written informed consent and HIPAA authorization
Who cannot join
- Diagnosis or past medical history of autoimmune disorder, including systemic lupus erythematosus, Crohn's disease, Sjogren's syndrome, multiple sclerosis, type 1 diabetes mellitus, Behcet's disease, and ankylosing spondylitis
- Current infection requiring medical treatment (note: if a prospective subject's infection resolves, they can be re-screened for trial inclusion)
- Concomitant treatment with systemic immunosuppressant drugs (see Table A1 in appendix for complete list)
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
About this study
This research aims to identify clinical strategies to manage adverse events during immune checkpoint inhibitor therapy by (1) determining the impact of checkpoint inhibitors on metabolism through major CYP enzymes and (2) identifying associations between pro-inflammatory cytokine concentrations and negative clinical outcomes during checkpoint inhibitor therapy.
Read the detailed description
The long-term goal of this research is to identify clinical strategies to manage adverse events during checkpoint inhibitor therapy. The research aims of the current project are (1) to determine the impact of checkpoint inhibitor therapy on the metabolism of CYP probe drugs and the risk for adverse events with CYP substrate drugs commonly prescribed to cancer patients and (2) to identify associations between pro-inflammatory cytokine concentrations and CYP probe drug metabolism before and during checkpoint inhibitor therapy. To investigate these aims, we plan to conduct a two-phase crossover clinical drug interaction study in which a cocktail containing probe drugs for six CYP enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A) is administered to subjects before and after they initiate checkpoint inhibitor therapy. However, the kinetics of changes in pro-inflammatory cytokines during checkpoint inhibitor therapy are not well established, and this knowledge is critical to inform timing of the on-treatment phase of the clinical drug interaction study. Accordingly, this pilot study will investigate when blood concentrations of pro-inflammatory cytokines peak after initiation of checkpoint inhibitor therapy. Blood cytokine concentrations will be assayed at baseline, ~7 and ~14 days following the first checkpoint inhibitor cycle (± 2 days surrounding each timepoint), and at cycles 2, 3, and 4 based on the strongest current in vitro (7-14 days) and clinical evidence (21-42 days). In addition to plasma concentrations of pro-inflammatory cytokines, the study will also assay plasma concentrations of immune checkpoint inhibitors, co-administered CYP substrates, and perform genetic sequencing to assess associations between these variables and clinical outcomes, including the development of immune-related adverse events, the potential for drug-drug interactions with CYP substrates, and checkpoint inhibitor treatment response.
- Keywords
- Checkpoint inhibitor, cytokines
- Medical subject headings
- Melanoma, Gastrointestinal Neoplasms, Urogenital Neoplasms, Sarcoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Increases in pro-inflammatory cytokines
Determine the time course of increases in pro-inflammatory cytokines during treatment with immune checkpoint inhibitor regimens, via plasma cytokine concentrations present in blood samples.
Measured: From baseline (day -30) up to cycle 4 (day 126)
Populations of activated T cells
Measured: From baseline (day -30) up to cycle 4 (day 126)
Secondary outcomes (6)
Increases in other cytokines
Determine the time course of increases in other cytokines during treatment with immune checkpoint inhibitor regimens, including anti-inflammatory cytokines (e.g., IL-10, TGF-β) present in blood samples.
Measured: From baseline (day -30) up to cycle 4 (day 126)
Plasma concentrations of immune checkpoint inhibitors
Assess on-treatment concentrations of immune checkpoint inhibitors
Measured: From baseline (day -30) up to cycle 4 (day 126)
Plasma concentrations of co-administered CYP substrate medications
Assess baseline and on-treatment concentrations of co-administered CYP substrate medications
Measured: From baseline (day -30) up to cycle 4 (day 126)
The development of immune-related adverse events
Immune-related adverse events will be assessed via patient survey at all study visits
Measured: From baseline (day -30) up to cycle 4 (day 126)
The development of adverse drug events attributable to co-administered CYP substrate medications
Adverse drug events attributable to co-administered CYP substrate medications will be assessed via patient survey at all study visits
Measured: From baseline (day -30) up to cycle 4 (day 126)
Checkpoint inhibitor treatment response
Checkpoint inhibitor treatment response will be collected retrospectively from the electronic health record
Measured: From treatment initiation (day 0) until the time of the treatment response event or the end of the study evaluation period (maximum of 2 years from the date of treatment initiation).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2023
- Study start7 Sep 2023
- Primary completion20 Jan 2025
- Study completion20 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Tyler Andrew Shugg, Indiana University
- Investigators
- Tyler Shugg, PharmD, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05707286
- Sponsor's protocol ID
- CPHR-IIR-CYTOKINE
- Other IDs
- K23GM147805
- Acronym
- ICI-PICK
- Status last verified
- Jan 2026
- First submitted
- 20 Jan 2023
- Last updated
- 7 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT05707286
- Acronym / sponsor ID
- ICI-PICK / CPHR-IIR-CYTOKINE
- Keywords
- Checkpoint inhibitor, cytokines
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 7 Sep 2023 (actual)
- Primary completion
- 20 Jan 2025 (actual)
- Study completion
- 20 Jan 2025 (actual)
- First posted
- 31 Jan 2023 (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.
This research aims to identify clinical strategies to manage adverse events during immune checkpoint inhibitor therapy by (1) determining the impact of checkpoint inhibitors on metabolism through major CYP enzymes and (2) identifying associations between pro-inflammatory cytokine concentrations and negative clinical outcomes during checkpoint inhibitor therapy.
Detailed description
The long-term goal of this research is to identify clinical strategies to manage adverse events during checkpoint inhibitor therapy. The research aims of the current project are (1) to determine the impact of checkpoint inhibitor therapy on the metabolism of CYP probe drugs and the risk for adverse events with CYP substrate drugs commonly prescribed to cancer patients and (2) to identify associations between pro-inflammatory cytokine concentrations and CYP probe drug metabolism before and during checkpoint inhibitor therapy. To investigate these aims, we plan to conduct a two-phase crossover clinical drug interaction study in which a cocktail containing probe drugs for six CYP enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A) is administered to subjects before and after they initiate checkpoint inhibitor therapy. However, the kinetics of changes in pro-inflammatory cytokines during checkpoint inhibitor therapy are not well established, and this knowledge is critical to inform timing of the on-treatment phase of the clinical drug interaction study. Accordingly, this pilot study will investigate when blood concentrations of pro-inflammatory cytokines peak after initiation of checkpoint inhibitor therapy. Blood cytokine concentrations will be assayed at baseline, ~7 and ~14 days following the first checkpoint inhibitor cycle (± 2 days surrounding each timepoint), and at cycles 2, 3, and 4 based on the strongest current in vitro (7-14 days) and clinical evidence (21-42 days). In addition to plasma concentrations of pro-inflammatory cytokines, the study will also assay plasma concentrations of immune checkpoint inhibitors, co-administered CYP substrates, and perform genetic sequencing to assess associations between these variables and clinical outcomes, including the development of immune-related adverse events, the potential for drug-drug interactions with CYP substrates, and checkpoint inhibitor treatment response.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults diagnosed with solid cancers and initiating therapy with an immune checkpoint inhibitor
Key inclusion criteria (3 listed)
- ≥ 18 years old at the time of informed consent
- Diagnosed with non-small cell lung cancer (NSCLC) OR melanoma AND initiating therapy with single agent or combination therapy that includes an immune checkpoint inhibitor, (e.g., atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab)
- Ability to provide written informed consent and HIPAA authorization
Key exclusion criteria (3 listed)
- Diagnosis or past medical history of autoimmune disorder, including systemic lupus erythematosus, Crohn's disease, Sjogren's syndrome, multiple sclerosis, type 1 diabetes mellitus, Behcet's disease, and ankylosing spondylitis
- Current infection requiring medical treatment (note: if a prospective subject's infection resolves, they can be re-screened for trial inclusion)
- Concomitant treatment with systemic immunosuppressant drugs (see Table A1 in appendix for complete list)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Increases in pro-inflammatory cytokines
Time frame: From baseline (day -30) up to cycle 4 (day 126)
Determine the time course of increases in pro-inflammatory cytokines during treatment with immune checkpoint inhibitor regimens, via plasma cytokine concentrations present in blood samples.
Populations of activated T cells
Time frame: From baseline (day -30) up to cycle 4 (day 126)
6 secondary outcomes
Increases in other cytokines
Time frame: From baseline (day -30) up to cycle 4 (day 126)
Plasma concentrations of immune checkpoint inhibitors
Time frame: From baseline (day -30) up to cycle 4 (day 126)
Plasma concentrations of co-administered CYP substrate medications
Time frame: From baseline (day -30) up to cycle 4 (day 126)
The development of immune-related adverse events
Time frame: From baseline (day -30) up to cycle 4 (day 126)
The development of adverse drug events attributable to co-administered CYP substrate medications
Time frame: From baseline (day -30) up to cycle 4 (day 126)
Checkpoint inhibitor treatment response
Time frame: From treatment initiation (day 0) until the time of the treatment response event or the end of the study evaluation period (maximum of 2 years from the date of treatment initiation).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2026.
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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.
Tyler Shugg, PharmD, PhD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma and Gastrointestinal Neoplasms, run by Indiana University at 1 site in United States.
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 3 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: finished, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increases in pro-inflammatory cytokines (time frame: From baseline (day -30) up to cycle 4 (day 126)). 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?
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 7 Jan 2026; AzTrials last refreshed its copy on 1 Nov 2026.