Gastrointestinal NeoplasmsEarly Phase 1NCT07389525
Immune Checkpoint Inhibitor (ICI)-Drug-Drug Interaction (DDI) Study
A Early Phase 1 study testing ICI Therapy in people with Gastrointestinal Neoplasms and Genitourinary Cancer, run by Indiana University at 1 site in United States.
Trial summary
Immune checkpoint inhibitors (ICIs) (also called "immunotherapy") are an effective family of anti-cancer drugs, but they can cause serious side effects. Some evidence suggests these side effects might happen because ICIs interact with other drugs that you may already be taking, making those drugs work differently, or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Neoplasms, Genitourinary Cancer, Thoracic Cancer
- What is being tested?
- ICI Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2026to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- ≥ 18 years old at the time of informed consent
- Diagnosed with cancer AND initiating therapy with single agent or combination therapy that includes an immune checkpoint inhibitor (e.g., atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, relatlimab, tremelimumab)
- Ability to provide written informed consent and HIPAA authorization
Who cannot join
- Actively pregnant or breastfeeding
- Body weight less than 50 kg or a BMI >35
- Low baseline hemoglobin, defined as <10 g/dL
- Note: if a prospective patient's hemoglobin returns to the normal range, they can be re-screened for trial inclusion)
- Past medical history of chronic liver disease, signs and symptom of liver disease (e.g., jaundice, ascites), or aspartate aminotransferase >96 U/L, alanine aminotransferase > 80 IU/L, alkaline phosphatase >260 U/L, or total bilirubin > 2.6 mg/dL
- Note: if a prospective patient's liver function tests return to the normal ranges, they can be re-screened for trial inclusion)
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- Past medical history of chronic kidney disease, signs and symptom of kidney disease (e.g., decreased urine output, swelling in feet and ankles), or estimated glomerular filtration rate <45 mL/minute/1.73 m2 BSA
- Note: if a prospective patient's kidney function returns to the normal range, they can be re-screened for trial inclusion)
- Poor performance status that makes it unlikely the patient will complete 3 cycles of immune checkpoint inhibitor (at the treating oncologist's discretion)
- 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
- History of intolerance, allergic reaction, or hypersensitivity to any of the study drugs (tizanidine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam, rosuvastatin)
- Current infection requiring medical treatment (note: if a prospective patient's infection resolves, they can be re-screened for trial inclusion)
- Concomitant treatment with systemic immunosuppressant drugs (see Appendix 3 for list)
- Note: patients may be re-screened for trial eligibility if they discontinue any exclusionary drugs for ≥7 days prior to Study Visit 1
- Concomitant treatment with a CYP/transporter probe cocktail drug or strong inhibitors, inducers, or agents that affect the pharmacokinetics of the relevant CYP enzymes or drug transporters (see Appendix 4 for list)
- Note: patients may be re-screened for trial eligibility if they discontinue any exclusionary drugs for ≥7 days prior to Study Visit 1
- Are unwilling/unable to avoid drugs of abuse, tobacco products or marijuana, or consuming more than 2 alcoholic drinks per day during the study
- Inability to take oral medication
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
Ross Robinson, 317-381-1426, rossrobi@iu.edu
Tyler Shugg, MD
About this study
Official title: Assessment of Drug-Drug Interactions Between Immune Checkpoint Inhibitors and Cytochrome P450 Substrates: Immune Checkpoint Inhibitor (ICI)-Drug-Drug Interaction (DDI) Study
Immune checkpoint inhibitors (ICIs) (also called "immunotherapy") are an effective family of anti-cancer drugs, but they can cause serious side effects. Some evidence suggests these side effects might happen because ICIs interact with other drugs that you may already be taking, making those drugs work differently, or causing more side effects. The purpose of this study is to see whether ICIs impact how the liver processes other drugs. To do this, participants will be given a probe cocktail of 7 different FDA-approved drugs that are processed in different ways in the liver.
Read the detailed description
Findings suggest that adverse events during checkpoint inhibitor therapy may, in part, be caused by drug-drug interactions that increase the risk of adverse events with co-administered medications. Identifying these novel drug-drug interactions will likely inform clinical strategies to reduce adverse events during checkpoint inhibitor therapy and enhance their clinical benefits.
This current research aims to systematically explore the impact of ICIs on CYP/transporter function and the associated risks for adverse events, thereby informing clinical strategies to mitigate these risks and optimize the therapeutic benefits of checkpoint inhibitors. By employing a rigorous crossover drug-drug interaction design, this study seeks to enhance understanding of drug interactions during ICI therapy, ultimately improving patient outcomes in oncology.
The long-term goal of this research is to find ways to manage adverse events that occur during treatment with ICIs. The research has two main aims:
- To understand how ICI therapy affects the metabolism of certain drugs named CYP/transporter probe drugs and to also understand the risk of side effects from commonly prescribed drugs that are affected by these enzymes and transporters in cancer patients.
- To examine the relationship between levels of pro-inflammatory cytokines (signaling molecules involved in inflammation) and how well these probe drugs are metabolized before and during ICI therapy.
A two-phase clinical study will be conducted to achieve these aims: patients will be given seven different probe drugs that interact with key enzymes and transporters (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A, BCRP, and SLCO1B1) both before they start ICI treatment and after they have begun therapy.
Adverse events will be assessed by looking at how changes in the function of these enzymes and transporters affect the metabolism of drugs that cancer patients commonly use. Special computer models, known as physiologically-based pharmacokinetic (PBPK) models, will be used to simulate how these drugs behave in the body and predict potential serious adverse events.
- Being tested
- ICI Therapy
- Keywords
- cytokines, immune checkpoint inhibitor
- Medical subject headings
- Gastrointestinal Neoplasms, Urogenital Neoplasms, Sarcoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICI TherapyDrug
Low dose of a cocktail of probe substrates for eight major CYP enzymes/drug transporters.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | CYP enzyme/drug transporter probe substrates administered at two study visits: one before initiation of ICI therapy and one while on therapy. Receives: Drug: ICI Therapy |
| Cohort 2 | Experimental | CYP enzyme/drug transporter probe substrates administered at one study visit: during ICI therapy. Receives: Drug: ICI Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma concentrations from drug exposure during ICI therapy
Measured: baseline (before start of ICI therapy) up to day 84
Toxicity concentrations for CYP/transporter substrate drugs in plasma
Measured: baseline (day before Cycle 1 start) up to day 84
Associations between pro-inflammatory cytokine concentrations and CYP/transporter probe drug concentrations in plasma
Measured: baseline (day before Cycle 1 start) up to day 84
Secondary outcomes (5)
Assess associations between T cells populations and CYP/transporter probe drug concentrations
Peripheral blood mononuclear cells (PBMCs)
Measured: baseline (day before Cycle 1 start) up to day 84
Concentrations of endogenous biomarkers
Plasma or urine
Measured: baseline (day before Cycle 1 start) up to day 84
CYP/transporter endogenous biomarker concentrations
Plasma or urine correlated with plasma concentrations of pro-inflammatory cytokines
Measured: baseline (day before Cycle 1 start) up to day 84
Correlation of concentration of population of activated T cells and CYP/transporter endogenous biomarkers
Plasma or urine
Measured: baseline (day before Cycle 1 start) up to day 84
CYP/transporter substrate-related adverse events and immune related (ir) adverse events
assessed through surveys given to participants
Measured: Baseline (before starting ICI cycle 1) and study visit 2 (up to day 84)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2026
- Study startSep 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal NeoplasmsStudies 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tyler Andrew Shugg, Indiana University
- Investigators
- Tyler Shugg, MD, Principal investigator, IUSCCC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07389525
- Sponsor's protocol ID
- PHARM-IUSCCC-0938
- Status last verified
- Jul 2026
- First submitted
- 29 Jan 2026
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Drug-Drug Interactions Between Immune Checkpoint Inhibitors and Cytochrome P450 Substrates: Immune Checkpoint Inhibitor (ICI)-Drug-Drug Interaction (DDI) Study
- ClinicalTrials.gov ID
- NCT07389525
- Acronym / sponsor ID
- PHARM-IUSCCC-0938
- Keywords
- cytokines, immune checkpoint inhibitor
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 5 Feb 2026 (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.
Immune checkpoint inhibitors (ICIs) (also called "immunotherapy") are an effective family of anti-cancer drugs, but they can cause serious side effects. Some evidence suggests these side effects might happen because ICIs interact with other drugs that you may already be taking, making those drugs work differently, or causing more side effects. The purpose of this study is to see whether ICIs impact how the liver processes other drugs. To do this, participants will be given a probe cocktail of 7 different FDA-approved drugs that are processed in different ways in the liver.
Detailed description
Findings suggest that adverse events during checkpoint inhibitor therapy may, in part, be caused by drug-drug interactions that increase the risk of adverse events with co-administered medications. Identifying these novel drug-drug interactions will likely inform clinical strategies to reduce adverse events during checkpoint inhibitor therapy and enhance their clinical benefits.
This current research aims to systematically explore the impact of ICIs on CYP/transporter function and the associated risks for adverse events, thereby informing clinical strategies to mitigate these risks and optimize the therapeutic benefits of checkpoint inhibitors. By employing a rigorous crossover drug-drug interaction design, this study seeks to enhance understanding of drug interactions during ICI therapy, ultimately improving patient outcomes in oncology.
The long-term goal of this research is to find ways to manage adverse events that occur during treatment with ICIs. The research has two main aims:
- To understand how ICI therapy affects the metabolism of certain drugs named CYP/transporter probe drugs and to also understand the risk of side effects from commonly prescribed drugs that are affected by these enzymes and transporters in cancer patients.
- To examine the relationship between levels of pro-inflammatory cytokines (signaling molecules involved in inflammation) and how well these probe drugs are metabolized before and during ICI therapy.
A two-phase clinical study will be conducted to achieve these aims: patients will be given seven different probe drugs that interact with key enzymes and transporters (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A, BCRP, and SLCO1B1) both before they start ICI treatment and after they have begun therapy.
Adverse events will be assessed by looking at how changes in the function of these enzymes and transporters affect the metabolism of drugs that cancer patients commonly use. Special computer models, known as physiologically-based pharmacokinetic (PBPK) models, will be used to simulate how these drugs behave in the body and predict potential serious adverse events.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: ICI TherapyCYP enzyme/drug transporter probe substrates administered at two study visits: one before initiation of ICI therapy and one while on therapy. |
| Cohort 2 | Experimental | Drug: ICI TherapyCYP enzyme/drug transporter probe substrates administered at one study visit: during ICI therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ≥ 18 years old at the time of informed consent
- Diagnosed with cancer AND initiating therapy with single agent or combination therapy that includes an immune checkpoint inhibitor (e.g., atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, relatlimab, tremelimumab)
- Ability to provide written informed consent and HIPAA authorization
Key exclusion criteria (18 listed)
- Actively pregnant or breastfeeding
- Body weight less than 50 kg or a BMI >35
- Low baseline hemoglobin, defined as <10 g/dL
- Past medical history of chronic liver disease, signs and symptom of liver disease (e.g., jaundice, ascites), or aspartate aminotransferase >96 U/L, alanine aminotransferase > 80 IU/L, alkaline phosphatase >260 U/L, or total bilirubin > 2.6 mg/dL
- Past medical history of chronic kidney disease, signs and symptom of kidney disease (e.g., decreased urine output, swelling in feet and ankles), or estimated glomerular filtration rate <45 mL/minute/1.73 m2 BSA
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 |
|---|---|---|
| ICI TherapyLow dose of a cocktail of probe substrates for eight major CYP enzymes/drug transporters. | Drug | Cohort 1, Cohort 2 |
Primary outcome
Change in plasma concentrations from drug exposure during ICI therapy
Time frame: baseline (before start of ICI therapy) up to day 84
Toxicity concentrations for CYP/transporter substrate drugs in plasma
Time frame: baseline (day before Cycle 1 start) up to day 84
Associations between pro-inflammatory cytokine concentrations and CYP/transporter probe drug concentrations in plasma
Time frame: baseline (day before Cycle 1 start) up to day 84
5 secondary outcomes
Assess associations between T cells populations and CYP/transporter probe drug concentrations
Time frame: baseline (day before Cycle 1 start) up to day 84
Concentrations of endogenous biomarkers
Time frame: baseline (day before Cycle 1 start) up to day 84
CYP/transporter endogenous biomarker concentrations
Time frame: baseline (day before Cycle 1 start) up to day 84
Correlation of concentration of population of activated T cells and CYP/transporter endogenous biomarkers
Time frame: baseline (day before Cycle 1 start) up to day 84
CYP/transporter substrate-related adverse events and immune related (ir) adverse events
Time frame: Baseline (before starting ICI cycle 1) and study visit 2 (up to day 84)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 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.
Tyler Shugg, MD principal investigator
IUSCCC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ICI Therapy in people with Gastrointestinal Neoplasms and Genitourinary Cancer, 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 18 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: opening soon, as of the sponsor's last update on 15 Jul 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ross Robinson (317-381-1426, rossrobi@iu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma concentrations from drug exposure during ICI therapy (time frame: baseline (before start of ICI therapy) up to day 84). The study lists 3 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 15 Jul 2026.