Optimizing Ancillary Therapies With Immune Checkpoint Inhibitors for Solid Tumors (OAT ICI) (OAT ICI)

Optimizing Ancillary Therapies (Acetaminophen, Cannabis, Antihistamines, and NSAIDS) With Immune Checkpoint Inhibitors for Solid Tumors (OAT ICI)

This study evaluates whether optimization of ancillary therapies can improve the efficacy of immune checkpoint therapy in participants with solid tumors. The ancillary therapies being optimized include the avoidance of daily acetaminophen and cannabis/THC/CBD while prescribing aspirin and loratadine. The goal is to see if optimizing these four drugs can improve the efficacy of the treatment compared to a matched historical control.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Asprin; Drug: Loratadine; Behavioral: Acetaminophen Avoidance; Behavioral: THC Avoidance

Detailed Description

There are multiple reports of ancillary drugs impacting the efficacy of immune checkpoint inhibitor therapy. However, there are no prospective studies evaluating the potential benefit of optimizing multiple ancillary therapies in a prospective study. To address this gap in knowledge the approach is to compare two groups; the first group is a prospective interventional population consisting of 98 solid tumor patients who have radiologically measurable cancer which are scheduled to receive immunotherapy as part of the participant's cancer treatment. Enrolled patients will be asked to avoid daily acetaminophen and the use of cannabis/THC/CBD. The participants will also be prescribed aspirin 162 mg (2 x 81 mg baby aspirin) and loratadine 10 mg to be taken once daily for 126 days. Collectively, optimizing these 4 drugs is called the OAT protocol. Once the prospective patient enrollment is complete, a historical control will be created to match patients based on their cancer, the treatment regimen, line of therapy, performance status, and age. The control group will not have received the OAT protocol optimization. The primary endpoint of the trial will be response rate at 18 weeks. Other efficacy endpoints include progression free survival and overall survival at 12 months. Safety and toxicity endpoints include those associated with aspirin and loratadine as well as the rate of immune-related adverse events. The study will also capture drug discontinuation, including ICI therapy as a measure of toxicity. Lastly, the study will explore the efficacy of the OAT protocol in different populations based on disease, smoking status, genetics, and cytokines. The hypothesis is that optimizing these therapies will increase response rates by at least 15% compared to the controls.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Val Adams; Phone Number: 8592575202; Email: val.adams@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Solid tumor patients with measurable disease. Including patients with early stage and advanced stage cancer.
• Patients who are to get neoadjuvant or induction therapy prior to planned surgery or radiation are included if definitive therapy is planned to occur at least 18 weeks after ICI initiation.
• Treatment plan includes an immune checkpoint inhibitor (PD1 or PD-L1 inhibitor) as standard of care. Standard of care will be determined by referring to the NCCN guidelines. For rare situations where a disease is not found in the NCCN guideline, the treatment must be considered standard of care at the MCC.
• ECOG Performance Status 0-3.
• Life expectancy of at least 3 months.
• Adequate hematologic, renal and hepatic function based on institutional standards.
• Must be willing to stop/not start daily acetaminophen during the study period
• Must be willing to stop/not start THC-containing agent (e.g., medical or recreational marijuana, CBD) during the study period
• Patients willing to take a second-generation antihistamine (loratadine) and an NSAID (aspirin). Patients already taking a daily antihistamine and/or NSAID can participate and will continue the class of drug already being taken
• Ability to understand and the willingness to follow study procedures, including urine testing for THC.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Contraindication to immunotherapy, aspirin, or loratadine (including patients on blood thinners or antiplatelet agents that pose a high risk of bleeding based on the treating oncologist's opinion)
• History of allergic reactions attributed to loratadine or aspirin (true allergy, not intolerance)
• Known immunocompromised patients; defined as disease or drug related. This includes solid organ transplant patients, patients with active human immunodeficiency virus (detectable disease within the last 60 days), and those with autoimmune diseases on immune modulating drugs (disease modifying agents or steroids at a prednisone equivalent dose > 10 mg daily).
• Early-stage disease patients who are scheduled for definitive therapy in less than 126 days from treatment initiation
• Patients must not have had prior ICIs for advanced disease except as neoadjuvant + adjuvant therapy. Patients with recurrence after definitive therapy may have had prior ICIs for earlier stage disease if it was > 6 months since the last dose.
• Patients on an interventional cancer study
• History or evidence of any other clinically significant condition that, in the opinion of the investigator or treating physician, would pose a risk to subject safety or interfere with study procedures, evaluation or completion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OAT ICI; Participants with solid tumors receiving standard-of-care immune checkpoint inhibitor therapy will follow the OAT ICI protocol, which includes use of loratadine and aspirin (or continuation of an equivalent antihistamine/NSAID), avoidance of acetaminophen, and avoidance of THC-containing products.	Drug: Asprin; Participants will receive Aspirin or continue an equivalent NSAID as part of the OAT ICI protocol while receiving standard-of-care immune checkpoint inhibitor therapy.; Drug: Loratadine; Participants will receive Loratadine or continue an equivalent antihistamine as part of the OAT ICI protocol while receiving standard-of-care immune checkpoint inhibitor therapy.; Behavioral: Acetaminophen Avoidance; Participants will be instructed to avoid acetaminophen-containing products during immune checkpoint inhibitor therapy as part of the OAT ICI protocol.; Behavioral: THC Avoidance; Participants will be instructed to avoid THC-containing products during immune checkpoint inhibitor therapy as part of the OAT ICI protocol.
No Intervention: Matched Historical Control; Retrospective matched controls identified from UK Healthcare EHR and Kentucky Cancer Registry data. Controls will be matched to enrolled participants by tumor type, disease stage, treatment regimen, line therapy, age group and ECOG performance status. Historical controls will not receive the OAT ICI protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18- Week Response Rate	To determine whether the OAT protocol improves therapeutic response to immune checkpoint inhibitor-containing regimens compared with matched historical controls, as measured by 18-week response rate.	18 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival by Disease Cohort	Progression-free survival among participants with lung cancer, head and neck cancer, bladder cancer, melanoma, and renal cell carcinoma compared with matched historical controls.	12 Months
Response Rate by Disease Cohort	Response rate (RECIST) at 18 weeks among participants with lung cancer, head and neck cancer, bladder cancer, melanoma, and renal cell carcinoma compared with matched historical controls	18 Weeks
Overall Survival	Overall survival at 12 months among participants receiving the OAT ICI protocol compared with matched historical controls.	12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Immune Cell Populations	T-cell subsets (including regulatory T cells [Tregs] and T-helper 17 [Th17] cells, monocytes, neutrophils at baseline, 9 and 18 weeks. Associations between baseline values and changes over time with response rate will be evaluated.	Baseline, 9 Weeks and 18 Weeks
Changes in Cytokine Profile	Cytokine profiles, including inerleukin-10 (IL-10) and histamine concentrations, measured at baseline, 9 and 18 weeks. Associations between baseline values and changes over time with response rate will be evaluated.s.	Baseline, 9 Weeks and 18 Weeks
Response Rate by Tumor Histology	Response rate stratified by tumor histology including adenocarcinoma, squamous cell carcinoma, and other histologic subtypes.	18 Weeks
Response Rate by Smoking Status and Genetic Profile	Association of response rate with smoking status and genetic factors, including tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) expression levels, using genetic data obtained from standard of care next-generation sequencing.	18 Weeks
Response Rate by Concurrent Ancillary Therapies	Association between response rate and use of other ancillary therapies that may affect immune checkpoint inhibitor effectiveness, including vaccines, proton pump inhibitors (PPIs), antibiotics and other concomitant treatments.	18 Weeks

Collaborators and Investigators

• Sponsor: Val Adams

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Piperidines; Dibenzocycloheptenes; Benzocycloheptenes; Cyproheptadine; Loratadine; acetylsalicylic acid lysinate
• Other Study ID Numbers: 114969

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes