NCT05541016

De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA

Recruiting now Phase 2 Last updated 4 November 2025

What this trial tests

Phase 2 trial testing Biospecimen Collection in Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 in 455 participants. Currently enrolling.

Timeline

21 February 2023

Primary endpoint
1 August 2028

1 August 2029

Quick facts

Lead sponsor	Mayo Clinic
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	455
Start date	21 February 2023
Primary completion	1 August 2028
Estimated completion	1 August 2029
Sites	3 locations across United States

Drugs / interventions tested

• Biospecimen Collection — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Computed Tomography
• Diffusing Alpha-emitter Radiation Therapy
• Docetaxel (Docetaxel) — full drug profile →
• Intensity-Modulated Proton Therapy
• Intensity-Modulated Radiation Therapy
• Magnetic Resonance Imaging
• Modified Barium Swallow Study
• Observation Activity
• Positron Emission Tomography
• Quality-of-Life Assessment
• Questionnaire

Conditions studied

• Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 — all drugs for Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 →
• Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 — all drugs for Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 →
• Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 — all drugs for Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 →
• Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma — all drugs for Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma →

Sponsor

Mayo Clinic

Who can join

18 and older, any sex, with Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 or Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This phase II trial examines the use of blood-based biomarkers is to help inform decision making for treatment and radiation therapy for patients with human papillomavirus (HPV) positive oropharyngeal squamous cell cancers. The standard treatments for head and neck cancers are radiation therapy with chemotherapy or surgery potentially followed by radiation therapy with or without chemotherapy. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving chemotherapy along with radiation may kill more tumor cells. However, the cancer can recur or can spread to other parts of the body and all treatments can be associated with side effects. The purpose of this study is to evaluate a blood-based biomarker, using the NavDx testing device, for head and neck cancers in order to see if it can help improve selection of the intensity of treatment in order to best balance the side effects of treatment with the goal of decreasing cancer recurrence. This test could aid in early detection of recurrence and salvage therapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.
   Aguayo F, Perez-Dominguez F, Osorio JC, Oliva C, et al · · 2023 · cited 27× · PMID 37237486 · DOI 10.3390/biology12050672
2. Circulating Human Papillomavirus DNA in Head and Neck Squamous Cell Carcinoma: Possible Applications and Future Directions.
   Adilbay D, Lele S, Pang J, Asarkar A, et al · · 2022 · cited 13× · PMID 36497430 · DOI 10.3390/cancers14235946
3. ctDNA and Recurrence Risk for Adjuvant De-Escalation in HPV-Positive Oropharyngeal Carcinoma: A Secondary Analysis of the DART Phase 3 Randomized Clinical Trial.
   Routman DM, Van Abel KM, Price KA, Moore EJ, et al · · 2025 · cited 8× · PMID 40402484 · DOI 10.1001/jamaoto.2025.0903
4. Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy-A Systematic Review.
   Schanne DH, Koch A, Elicin O, Giger R, et al · · 2022 · cited 6× · PMID 36552043 · DOI 10.3390/biomedicines10123288
5. Tumor-Derived Exosomes and the Role of Liquid Biopsy in Human Papillomavirus Oropharyngeal Squamous Cell Carcinoma.
   Allevato MM, Smith JD, Brenner MJ, Chinn SB. · · 2023 · cited 5× · PMID 37471614 · DOI 10.1097/ppo.0000000000000671
6. De-Escalation Strategies in HPV-Associated Oropharynx Cancer: A Historical Perspective with Future Direction.
   Wu C, Kuzmin P, Julian R. · · 2024 · cited 4× · PMID 39123461 · DOI 10.3390/cancers16152733
7. Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer.
   Muniz IAF, Araujo M, Bouassaly J, Farshadi F, et al · · 2024 · cited 4× · PMID 38612819 · DOI 10.3390/ijms25074009
8. Early Dynamics of Circulating Tumor HPV-DNA with Neoadjuvant Chemotherapy and Response-Adapted De-escalation in Human Papillomavirus-Associated Oropharyngeal Cancer.
   Rosenberg AJ, Izumchenko E, Juloori A, Katipally R, et al · · 2025 · cited 1× · PMID 40423530 · DOI 10.1158/1078-0432.ccr-25-0152