Immune Checkpoint Inhibitor (ICI)-Drug-Drug Interaction (DDI) Study

NCT07389525 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: PHARM-IUSCCC-0938
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Gastrointestinal Neoplasms; Genitourinary Cancer; Thoracic Cancer; Sarcoma; Melanoma

Keywords

cytokines; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (3)

• Change in plasma concentrations from drug exposure during ICI therapy

  baseline (before start of ICI therapy) up to day 84

• Toxicity concentrations for CYP/transporter substrate drugs in plasma

  baseline (day before Cycle 1 start) up to day 84

• Associations between pro-inflammatory cytokine concentrations and CYP/transporter probe drug concentrations in plasma

  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

  baseline (day before Cycle 1 start) up to day 84

• Concentrations of endogenous biomarkers

  baseline (day before Cycle 1 start) up to day 84

• CYP/transporter endogenous biomarker concentrations

  baseline (day before Cycle 1 start) up to day 84

• Correlation of concentration of population of activated T cells and CYP/transporter endogenous biomarkers

  baseline (day before Cycle 1 start) up to day 84

• CYP/transporter substrate-related adverse events and immune related (ir) adverse events

  Baseline (before starting ICI cycle 1) and study visit 2 (up to day 84)

Study Arms (2)

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.

Drug: ICI Therapy

Cohort 2

EXPERIMENTAL

CYP enzyme/drug transporter probe substrates administered at one study visit: during ICI therapy.

Drug: ICI Therapy

Interventions

ICI Therapy DRUG

Low dose of a cocktail of probe substrates for eight major CYP enzymes/drug transporters.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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
• 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)
• Concomitant treatment with systemic immunosuppressant drugs (see Appendix 3 for list)
• 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)
• 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

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Urogenital Neoplasms; Sarcoma; Melanoma

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Tyler Shugg, MD

  IUSCCC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ross Robinson

CONTACT

317-381-1426; rossrobi@iu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 5, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)