What randomized clinical trials are registered or ongoing testing mebendazole plus chemotherapy for specific cancers (e.g., colorectal, glioblastoma)?
Executive summary
Randomized evidence testing mebendazole (MBZ) combined with standard chemotherapy is extremely limited: a small, prospective randomized double‑blind placebo‑controlled trial in metastatic colorectal cancer (mCRC) has been registered (NCT03925662) and represents the clearest randomized test to date [1] [2], while most other human studies are early‑phase, nonrandomized safety or dose‑finding trials—notably a phase 1 study combining MBZ with temozolomide in high‑grade gliomas [3] and a phase 2a individualized‑dose trial in advanced gastrointestinal cancers [4].
1. The single small randomized colorectal trial that exists — design and scope
The colorectal study recorded as NCT03925662 is described in the literature as a prospective randomized double‑blind placebo‑controlled investigation enrolling 40 patients with metastatic colorectal cancer who received six cycles of bevacizumab plus FOLFOX4 as first‑line therapy with either MBZ or placebo added; this trial is the principal example of a randomized MBZ‑plus‑chemotherapy investigation in humans to date [1] [2].
2. Glioblastoma and brain cancer: phase 1 safety data, not randomized efficacy trials
Clinical work in brain tumors has focused on safety and feasibility rather than randomized efficacy: a Johns Hopkins phase 1 trial combined mebendazole with temozolomide in newly diagnosed high‑grade glioma patients under an IND and used custom MBZ formulations to assess tolerability at higher doses, concluding MBZ can be used safely with temozolomide in this context but without randomized efficacy data [3] [5].
3. Other human trials and their phases — small, early, and often nonrandomized
Beyond the glioma phase 1 and the colorectal randomized study, the clinical portfolio includes a phase 2a individualized‑dosing study in advanced gastrointestinal cancer that evaluated safety and preliminary efficacy of MBZ in that heterogeneous population; this trial was not a randomized chemotherapy‑combination efficacy trial but does add human safety and signal data [4].
4. Preclinical rationale that motivated trials — strong but not definitive
A broad preclinical literature shows MBZ has antiproliferative, anti‑angiogenic and multi‑target kinase effects across many cancer models and can cross the blood‑brain barrier, providing mechanistic rationale for combining it with standard chemotherapies in colon cancer, glioma and other tumors [6] [7] [8] [9] [10]. These laboratory and animal findings underpinned calls for small clinical trials or carefully regulated off‑label use, but authors and reviews stress the need for controlled human data to confirm benefit and safety [7] [11].
5. Caveats, contested claims and the misinformation problem
Claims circulating in integrative and promotional outlets that MBZ dramatically prolongs progression‑free survival when added to chemotherapy (for example, blanket statements of PFS rising from 3 to 9.25 months) are not supported by the peer‑reviewed randomized evidence provided here and appear to overstate limited trial results or anecdotal reports [12]; rigorous authors explicitly caution that there are still “no reports” documenting safety at the high doses sometimes advocated or efficacy from large randomized trials [3] [13].
6. Stakes and the path forward — what the clinical record actually shows
The aggregate clinical record is early and mixed: one small randomized colorectal trial is registered and represents the best current randomized test of MBZ plus chemotherapy [1] [2], while glioma work has established a tolerability foundation in phase 1 studies [3] [5] and other trials (phase 2a, dose‑finding) supply safety and signal data [4]; however, large randomized phase 2/3 trials testing MBZ as an adjunct to standard chemotherapy across tumor types have not yet been reported in the reviewed literature, leaving efficacy unproven despite compelling preclinical rationale [6] [7] [8].