Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
T
Tyler Shugg
Primary Investigator
Enrolling By Invitation
18 years and older
All
Phase
N/A
75 participants needed
1 Location
Brief description of study
What is the purpose of 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.
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office
Email: iutrials@iu.edu
Phone: (317) 278-5632
Detailed description of study
What will happen during the study?
1) The long-term goal of this research is to identify clinical strategies to manage adverse
events during checkpoint inhibitor therapy.
2) 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.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Non Small Cell Lung Cancer, Melanoma
-
Age: 18 Years
-
Gender: All
Inclusion Criteria:
- ≥ 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
Exclusion Criteria:
- 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)
Updated on
01 Aug 2024.
Study ID: CPHR-IIR-CYTOKINE, 14904
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