What are the full hematologic monitoring schedules (CBC frequency and stopping rules) used in registered mebendazole oncology trials (NCT01729260, NCT01837862, NCT03628079)?
Executive summary
The public record for the three mebendazole oncology trials contains explicit hematologic toxicity definitions for the adult high‑grade glioma Phase I trial (NCT01729260) but does not publish a complete, day‑by‑day CBC monitoring schedule or formal stopping rules for all three trials; the pediatric trial (NCT01837862) and the GI cancer trial (NCT03628079) list baseline/eligibility hematologic requirements and state that blood sampling will be used for safety/PK but do not disclose an explicit CBC frequency or prespecified hematologic dose‑modification algorithm in the provided sources [1] [2] [3] [4] [5].
1. The adult glioma Phase I trial: what is stated about hematologic toxicity and dose‑limiting events
The Phase I dose‑escalation trial at Johns Hopkins (NCT01729260) defined dose‑limiting toxicity (DLT) in clear CTCAE terms: any CTCAE v4.0 grade ≥4 hematologic toxicity or grade ≥3 nonhematologic toxicity within the first cycle constituted a DLT, and that definition guided escalation to the planned maximum dose when no hematologic DLTs were seen in cycle one (no DLTs were observed and dosing escalated to 200 mg/kg/day) [1] [2]. The published trial report also notes three grade‑3 hematologic events (neutropenia), one occurring with mebendazole alone, but explicitly states none exceeded grade‑3 so no hematologic dose reductions were required under the trial’s operational decisions as reported [2]. These are concrete, trial‑level stopping thresholds for hematologic DLTs, but they do not constitute a full monitoring schedule [1] [2].
2. The pediatric glioma trial: eligibility lab thresholds and absence of published CBC schedule
The pediatric Phase I/II trial at Cohen Children’s/other registries (NCT01837862) repeatedly emphasizes that participants must demonstrate adequate hematologic, renal, and liver function on laboratory testing as part of eligibility and safety screening, and frames mebendazole use as an adjunct to standard cytotoxic chemotherapy with longstanding clinical safety in humans [3] [4] [6]. However, the publicly available registry entries and secondary summaries in the sources supplied do not include a detailed CBC frequency (for example, pre‑cycle, weekly, or midcycle draws) nor a published hematologic stopping or dose‑modification algorithm in the excerpts provided [3] [4] [7]. Therefore one can report the trial’s reliance on baseline/ongoing lab adequacy without claiming a specific monitoring cadence that is not in the record available here.
3. The gastro‑oncology individualized‑dosing trial: PK sampling and safety checks but limited lab schedule detail
The Swedish phase 2a study tied to NCT03628079 describes a PK week followed by up to 16 weeks of treatment with individualized dosing to achieve target serum mebendazole concentrations and states that safety was assessed by clinical surveillance, CT imaging and blood sampling (CBCs implied by “blood sampling”) [5] [8]. The paper indicates individualized dose adjustments and safety monitoring, but the provided text does not enumerate how often complete blood counts were performed, nor does it present a prespecified hematologic stopping rule comparable to the DLT definition published for NCT01729260 [5]. The study design therefore signals active hematologic oversight without making the exact monitoring schedule or dose‑hold thresholds public in these excerpts.
4. What can and cannot be concluded from the record — and why the gaps matter
It is verifiable that NCT01729260 used CTCAE‑based hematologic DLT criteria (grade ≥4) to determine dose‑limiting hematologic toxicity [1] [2] and that both pediatric and GI trials required adequate baseline hematologic function and used blood sampling for safety [3] [4] [5]. What cannot be asserted from the provided sources is the full, operational CBC monitoring schedules (for example exact days or weekly cadence), nor detailed hematologic stopping or dose‑modification algorithms for NCT01837862 and NCT03628079; those details are either not present in the registry excerpts or were not included in the supplied publications [3] [4] [5]. This reporting limitation matters for clinicians or patients seeking actionable monitoring checklists and for safety comparisons across repurposing trials.
5. Context and alternative viewpoints: safety framing and possible motives
Investigators frame mebendazole as low‑risk and repurposed — the adult trial documented no hematologic DLTs in cycle one and only grade‑3 neutropenia events overall, supporting a narrative of tolerability that enabled dose escalation [2]. Critics or cautious clinicians might counter that combining mebendazole with myelosuppressive agents (temozolomide, carboplatin, vincristine) in pediatric or adult regimens increases the importance of explicit CBC schedules and dose‑modification rules, which are not fully public in these excerpts and therefore leave a gap in independent safety appraisal [3] [6]. The registries’ emphasis on baseline adequacy and blood sampling reflects legitimate safety practice but does not substitute for a published monitoring algorithm when assessing replication or off‑label use risks [4] [5].