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Pyrimethamine as an Inhibitor of NRF2 in HPV-unrelated Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT05678348 · View on ClinicalTrials.gov ↗
Study Summary
NRF2 activation, observed in up to 40% of head and neck squamous cell carcinoma (HNSCC) tumors, plays a critical role in tumor progression, metastasis, and radiation therapy resistance. The investigators have recently discovered that pyrimethamine (PYR) and its analogs have an inhibitory effect on NRF2 activity in vitro and in mouse models via inhibition of dihydrofolate reductase (DHFR). Pyrimethamine is an established drug that has been used for decades for treatment of protozoan infections and malaria. A growing body of research shows that it has potential antitumor activity, however its activity on growing human tumors has not been previously studied. The primary efficacy goal of this study is to evaluate the activity of pyrimethamine on human tumors as demonstrated by inhibition of DHFR and downregulation of NRF2 pathway activity. On-target inhibition of DHFR by pyrimethamine results in the stabilization and increased protein expression of human DHFR. The primary efficacy hypothesis of this study is that treatment with pyrimethamine will result in a 50% increase in DHFR protein within the tumor cells as measured by quantitative western blot analysis. Secondarily, among those tumors classified as NRF2-active on pre-treatment biopsy, the investigators hypothesize there will be a 50% reduction in NRF2 activity as measured by SureQuant targeted proteomic analysis.
Conditions Studied
Interventions
- DRUG Pyrimethamine
Study Locations (1)
Missouri
- Washington University School of Medicine — St Louis
Trial Details
| Field | Value |
|---|---|
| Enrollment Target | 22 participants |
| Start Date | 2023-08-03 |
| Est. Completion | 2025-08-04 |
| Phase | Early Phase 1 |
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Full Details on ClinicalTrials.gov ↗What the Registry Record Tells You About NCT05678348
The ClinicalTrials.gov registry entry for NCT05678348 describes a study currently listed as completed. It is categorized as Early Phase 1, which is the standard way researchers label where a study sits along the investigational pathway from early safety work through later efficacy and post-marketing evaluation. The registered enrollment target is 22 participants, a figure that helps gauge the scale of data the investigators plan to collect. The listed sponsor is Washington University School of Medicine, which has 1,036 total studies on file at ClinicalTrials.gov, and sponsors are the parties responsible for study design, oversight, and regulatory filings.
The record links to 2 conditions, with Head and Neck Cancer appearing as the primary indexed condition, and to 1 intervention — of which Pyrimethamine is the first listed. Interventions can include drugs, devices, procedures, behavioral programs, or observational arms, and each is tracked as a separate registry field so that downstream queries can filter accurately. When a trial lists multiple interventions, it usually reflects a multi-arm design or a comparison protocol rather than a single treatment being tested in isolation. The brief summary published in the registry is the clearest source of protocol intent and should be read before drawing conclusions from any sidebar tags.
Geographic footprint matters for practical reasons: NCT05678348 reports 1 study location spanning 1 distinct geographic area — top geographies include Missouri. A larger site network tends to correlate with broader recruitment capacity, but it does not imply anything about study quality, and site-level enrollment status can diverge from the overall registry status shown above. Every data point on this page comes from the public ClinicalTrials.gov dataset and is reproduced here for reference only; it is not a medical recommendation, an endorsement of the sponsor, or an invitation to enroll. Verify current status, eligibility criteria, and contact details directly at ClinicalTrials.gov, and discuss any participation decision with your own healthcare provider.
Frequently Asked Questions
What is clinical trial NCT05678348 about?
NCT05678348 is a clinical study titled "Pyrimethamine as an Inhibitor of NRF2 in HPV-unrelated Locally Advanced Head and Neck Squamous Cell Carcinoma". NRF2 activation, observed in up to 40% of head and neck squamous cell carcinoma (HNSCC) tumors, plays a critical role in tumor progression, metastasis, and radiation therapy resistance. The investigators have recently discovered that pyrimethamine (PYR) and its analogs have an inhibitory effect on N...
What is the current status of trial NCT05678348?
This trial is currently completed. It is a Early Phase 1 study. The enrollment target is 22 participants. The study started on 2023-08-03. Estimated completion is 2025-08-04.
What conditions does trial NCT05678348 study?
This clinical trial studies the following conditions: Head and Neck Cancer, Cancer of the Head and Neck. These conditions were identified from the trial registry and reflect the primary focus areas of the research.
What interventions are being tested in trial NCT05678348?
The interventions under investigation include: Pyrimethamine (DRUG). Each intervention is being evaluated for safety and efficacy as part of this clinical study.
Who is sponsoring clinical trial NCT05678348?
This trial is sponsored by Washington University School of Medicine, which has 1,036 total clinical trials registered on ClinicalTrials.gov. The sponsor is responsible for the study's design, funding, and regulatory compliance.
Where is trial NCT05678348 being conducted?
This trial has 1 study location across Missouri. Contact the study sites directly through ClinicalTrials.gov for enrollment availability.
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