What randomized clinical trials of ivermectin in cancer are currently registered and what are their designs and endpoints?
Executive summary
Only a single actively registered randomized or early-phase trial of ivermectin in human cancer patients is clearly documented in the available reporting: a phase I/II study combining oral ivermectin with anti‑PD‑1 immunotherapy for metastatic triple‑negative breast cancer (TNBC) (ClinicalTrials.gov NCT05318469 / Gateway for Cancer Research) [1] [2]. The broader literature and reviews emphasize that clinical evidence is scarce and most ivermectin anticancer work remains preclinical, leaving efficacy in humans unproven [3] [4] [5].
1. The lone registered trial and its structure: a phase I/II combination in metastatic TNBC
ClinicalTrials.gov lists NCT05318469 as a phase I/II study testing ivermectin in combination with balstilimab (an anti‑PD‑1 agent) in patients with metastatic TNBC, with the Gateway for Cancer Research describing the trial as designed to assess safety and to expand into a PD‑L1 negative cohort, signaling both dose‑finding and early efficacy evaluation [1] [2]. An ASCO abstract and a Journal of Clinical Oncology entry further summarize the study as focused on safety and efficacy endpoints in metastatic TNBC, reflecting the usual phase I/II objectives of determining tolerability and preliminary antitumor activity [6]. Trial logistics reported in later summaries specify oral ivermectin given on Days 1–3, 8–10, and 15–17 of each 21‑day cycle alongside IV balstilimab (450 mg) or pembrolizumab (200 mg) on Day 1, with treatment continuing up to 35 cycles or until progression or toxicity—details that underscore a combined immunotherapy‑repurposing rationale rather than monotherapy testing [7].
2. Endpoints spelled out (and what remains uncertain)
Public descriptions of NCT05318469 emphasize safety as the primary early endpoint, with efficacy signals assessed in expansion cohorts—typical readouts include adverse event profiles, dose‑limiting toxicities, and investigator‑assessed responses, although the precise primary and secondary endpoint text is not reproduced verbatim in the provided summaries [2] [6]. Reporting from meeting abstracts and trial registries implies evaluation of response and clinical benefit in PD‑L1 negative TNBC as a key objective but does not supply a definitive list of statistical endpoints (objective response rate, progression‑free survival, overall survival) within the provided snippets, so the exact formal endpoints must be confirmed directly in the full ClinicalTrials.gov protocol entry for NCT05318469 [1] [2] [6].
3. Other registered entries and the signal of scarcity
Searches and recent reviews repeatedly conclude there is only one active clinical trial testing ivermectin in cancer patients, despite dozens of preclinical studies and substantial internet interest; systematic mapping efforts and an Annals of Oncology review identified a single active trial (the TNBC study) and stressed the absence of human efficacy data to date [8] [3]. ClinicalTrials.gov does list other ivermectin‑named records (for example NCT04447235) but available snippets for that registration lack clear cancer trial design detail in the provided reporting, preventing definitive inclusion as a randomized cancer trial from these sources alone [9].
4. Why the trial exists and why caution is widespread
Preclinical literature documents multiple anticancer mechanisms for ivermectin—cell cycle effects, apoptosis induction, immune‑modulating activity and pathway inhibition—that motivate repurposing efforts and the combination with immune checkpoint inhibitors to “heat up” immunologically cold tumors [3] [4] [10]. At the same time, reviews warn that human clinical evidence is nearly non‑existent, ethical concerns about misinformation persist, and large randomized controlled trials demonstrating benefit are lacking, reinforcing the need for rigorous testing before clinical adoption [3] [11] [8].
5. Bottom line and reporting limitations
The best‑documented, actively recruiting/ongoing human cancer trial of ivermectin is the phase I/II combination trial in metastatic TNBC (NCT05318469), built to evaluate safety and early efficacy signals alongside PD‑1 blockade; reporting elsewhere and reviews consistently note only this single active oncology trial and emphasize that broader clinical proof is absent [1] [2] [6] [8]. The provided sources do not include the full trial protocol text or a complete, itemized list of formal primary/secondary endpoints, nor do they confirm additional randomized cancer trials; therefore the account above relies on the available registry entries, meeting abstracts, and reviews and acknowledges that definitive endpoint language should be read directly from the ClinicalTrials.gov protocol record [1] [6] [8].