Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy

NCT ID: NCT05707286

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 98 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-09-07
• Study Completion Date: 2025-01-20

Brief 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 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.

Conditions

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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. ≥ 18 years old at the time of informed consent

2. 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)

3. Ability to provide written informed consent and HIPAA authorization

Exclusion Criteria

1. 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

2. Current infection requiring medical treatment (note: if a prospective subject's infection resolves, they can be re-screened for trial inclusion)

3. Concomitant treatment with systemic immunosuppressant drugs (see Table A1 in appendix for complete list)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Tyler Andrew Shugg

Assistant Research Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tyler Shugg, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

K23GM147805

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CPHR-IIR-CYTOKINE

Identifier Type: -

Identifier Source: org_study_id