Ivermectin Combined With Immune Checkpoint Inhibition in Cancer (ICONIC)
ConditionSolid Tumor, Adult
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Florida
About this trial
Public awareness of ivermectin's purported anticancer properties has led to widespread off-label use. In a 2023 cross-sectional study in Loja, Ecuador, 19% of respondents reported using ivermectin as an adjunct to cancer treatment. However, clinical data remain virtually absent. To date, only one partially reported human study has investigated ivermectin in combination with anti-PD-1 therapy in patients with metastatic triple-negative breast cancer. Among the first nine treated patients, no treatment-related serious adverse events were observed, and the study remains ongoing.
Despite this growing interest, ivermectin's off-label use carries risks. For instance, Gilene et al. described a case of severe neurotoxicity in a patient with metastatic osteosarcoma receiving regorafenib, likely due to a pharmacokinetic interaction through CYP3A49. Moreover, the potential impact of ivermectin on the gut microbiome-a key modulator of immune checkpoint inhibitor (ICI) immunotherapy success or failure efficacy-remains poorly understood. As antibiotic exposure has been linked to diminished immunotherapy outcomes, ivermectin's antibiotic properties raise legitimate concerns about possible microbiome disruption. However, variables such as ivermectin dose, the duration of exposure, and the type of immunotherapy are each variables that remain poorly studied.
Taken together, these data underscore the urgency to prospectively evaluate ivermectin's immunologic effects in patients with cancer treated ICIs. Given ivermectin's wide availability, affordability, and public interest, rigorous clinical testing is crucial to determine whether it enhances-or potentially compromises-anticancer immunity while simultaneously assessing its safety to provide guidance for clinicians and patients.
This study will investigate the safety, pharmacodynamic effects, and potential for dose-responsive immune modulation of ivermectin given concurrently with immune checkpoint inhibitor therapy in adult subjects with solid tumors.
Eligibility criteria
Qualifiers
Histologically or clinically confirmed solid tumor malignancy for which the patient has been receiving an immune checkpoint inhibitor (ICI) as part of standard of care for ≥21 days prior to the first ivermectin dose, either alone or in combination with other systemic therapies. Both metastatic and (neo)adjuvant treatment settings are permitted.
Adults ≥ 18 years of age.
ECOG Performance Status of 0-2.
Subjects must be able to swallow oral medication.
Disqualifiers
Subjects who are currently taking, or have taken, ivermectin without a washout period prior to first treatment on study.
Subjects who have received their first dose of ICI therapy <21 days before the baseline visit.
Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug.
Subjects who are confirmed to be pregnant or breastfeeding.
Trial design
Treatments tested in this trial
- Intermediate-dose ivermectin
- High-dose ivermectin
Treatment groups
80 Participants
are divided into 2 treatment groupsLocations
Sponsors and collaborators
Source ClinicalTrials.gov