This phase II trial tests the effect of optimizing ancillary therapies (treatment used in addition to primary therapy) by using loratadine and aspirin and avoiding acetaminophen and tetrahydrocannabinol (THC)-containing products (cannabis, THC and cannabidiol [CBD]) in treating patients with solid tumors receiving immune checkpoint inhibitors (ICIs). Immunotherapy with monoclonal antibodies, such as ICIs, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Because ICIs target immune signals, not tumor signals, over-the-counter medications can alter the immune response and the effectiveness of ICIs. Acetaminophen, an analgesic, is a drug that reduces pain and fever (but not inflammation) has been shown to have a negative impact on the effectiveness of ICIs. THC is an active ingredient in marijuana. THC-containing medications are commonly used for symptom management and can suppress key immune functions critical for the success of ICI therapy. Loratadine, an antihistamine, works by blocking the action of histamine (a substance released during an allergic reaction or by tumor cells) and may reduce antitumor immune responses. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), is a drug that reduces pain, fever, inflammation, and blood clotting. It may also enhance the effectiveness of ICI therapy and improve the immune response. Optimizing use of loratadine and aspirin and avoiding the use of acetaminophen and THC-containing products may improve response in patients with solid tumors receiving ICI therapy compared to historical controls.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07661459.
Locations matching your search criteria
United States
Kentucky
Lexington
University of Kentucky/Markey Cancer CenterStatus: Active
Contact: Val Adams
Phone: 859-257-5202
PRIMARY OBJECTIVE:
I. To determine if the optimal ancillary therapies (OAT) Protocol (optimizing patient/participant use of acetaminophen, loratadine, aspirin, and cannabis/ THC/CBD containing therapies) will improve therapeutic responses to immunotherapy-containing regimens (monotherapy or combination therapy; all diseases) measured by 18-week response rate (RR), compared to matched historical controls.
SECONDARY OBJECTIVES:
I. Determine the efficacy in specific disease cohorts (lung cancer, head and neck cancer, bladder cancer, melanoma, and renal cell carcinoma) as measured by 18-week RR (Response Evaluation Criteria in Solid Tumors [RECIST]) as well as median and progression-free survival (PFS) during the first 12 months compared to controls.
II. Assess the impact on overall survival (OS) at 12-months for OAT ICI patients compared to the control arm.
III. Monitor safety and tolerability of the OAT protocol by measuring toxicity frequency and severity (additionally, the rate of immune checkpoint inhibitors [ICI] discontinuation due to toxicity compared to historical controls).
EXPLORATORY OBJECTIVES:
I. Evaluate immune cell populations: T-cell subsets (focus on regulatory T cells [Tregs] and TH17), monocytes, neutrophils at baseline, 9- and 18-weeks.
II. Evaluate cytokine profiles (interleukin [IL]-10 and histamine) at baseline, 9- and 18-weeks.
III. Evaluate if RR varies by histology (adenocarcinoma, squamous cell carcinoma, other).
IV. Determine if populations defined by smoking status or genetic mutation profiles, including tumor mutational burden (TMB) and PD-L1 expression levels impact RR (genetic data obtained from standard of care [SOC] next generation sequencing [NGS]).
V. Determine if other ancillary treatments thought to impact ICI effectiveness (vaccines, proton pump inhibitors [PPIs], antibiotics, etc.) have an impact on RR in the OAT protocol group.
OUTLINE:
Patients continue SOC ICI and receive aspirin orally (PO) once daily (QD) and loratadine PO QD for up to 18 weeks (126 days) in the absence of disease progression or unacceptable toxicity. Patients also receive counseling to avoid acetaminophen and cannabis/THC/CBD-containing products on study. Additionally, patients undergo imaging, as well as urine and blood sample collection throughout the study.
After completion of study treatment, patients are followed at 6, 9, and 12 months.
Lead OrganizationUniversity of Kentucky/Markey Cancer Center
Principal InvestigatorVal Adams
