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

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

NCT ID: NCT05707286

Condition: Non Small Cell Lung Cancer
Melanoma

Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung

Conditions: Keywords:
Checkpoint inhibitor
cytokines

Study type: Observational

Overall status: Recruiting

Study design:

Time perspective: Prospective

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.

Criteria for eligibility:

Study pop:
Adults diagnosed with solid cancers and initiating therapy with an immune checkpoint inhibitor

Sampling method: Probability Sample
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)

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Address:
City: Indianapolis
Zip: 46202
Country: United States

Status: Recruiting

Contact:
Last name: Ross Robinson, MS

Phone: (317)274-2744
Email: rossrobi@indiana.edu

Contact backup:
Last name: Tyler Shugg, PharmD, PhD

Start date: September 7, 2023

Completion date: March 2026

Lead sponsor:
Agency: Indiana University
Agency class: Other

Collaborator:
Agency: National Institute of General Medical Sciences (NIGMS)
Agency class: NIH

Source: Indiana University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05707286