Pyrimethamine as an Inhibitor of NRF2 in HPV-unrelated Locally Advanced Head and Neck Squamous Cell Carcinoma
Public ClinicalTrials.gov record NCT05678348. Field values are reproduced from the official study page; the official ClinicalTrials.gov record remains the source of truth for eligibility, enrollment, and contact information.
Data is sourced from official ClinicalTrials.gov public API records. Always review the official ClinicalTrials.gov record for the latest information.
Official title
Early Phase I Window of Opportunity Biomarker and Safety Trial to Test Pyrimethamine as an Inhibitor of NRF2 in HPV-unrelated, Locally Advanced Head and Neck Squamous Cell Carcinoma
Brief summary
Reproduced verbatim from the official ClinicalTrials.gov record. Not medical advice.
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.
Study identification
- NCT ID
- NCT05678348
- Recruitment status
- Completed
- Study type
- Interventional
- Phase
- Early Phase 1
- Enrollment
- 22 participants
Conditions and interventions
Conditions
Eligibility (public fields only)
- Age range
- 18 Years and older
- Sex
- All
- Healthy volunteers
- Healthy volunteers not accepted
This page does not interpret eligibility. Detailed inclusion and exclusion criteria are on the official ClinicalTrials.gov record.
Study timeline
- Start date
- Aug 2, 2023
- Primary completion
- Jul 10, 2025
- Completion
- Aug 3, 2025
- Last update posted
- Aug 16, 2025
2023 – 2025
United States locations
- U.S. sites
- 1
- U.S. states
- 1
- U.S. cities
- 1
| Facility | City | State | ZIP | Site status |
|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | — |
Site contact phone numbers, emails, and investigator names are intentionally not displayed here. Open the official ClinicalTrials.gov record for site contact information.
About this trial record page
- What this page shows
- Public field values for ClinicalTrials.gov record NCT05678348, including study identification, conditions, interventions, eligibility (age, sex, healthy volunteer), timeline, and U.S. site list.
- What this page does not do
- No medical advice, eligibility judgments, treatment recommendations, study quality scoring, or AI-generated medical summaries. No site contact phone numbers, emails, or investigator names.
- Where the data comes from
- Sourced from the official ClinicalTrials.gov public API. The official record is the source of truth.
- Last refresh
- Last update posted Aug 16, 2025 · Synced Sep 5, 2026
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Open the official record
The complete protocol, eligibility criteria, and contact information for NCT05678348 live on ClinicalTrials.gov.