Trial results for the HYHOPE study, investigating de-intensified hypofractionated radiation therapy for HPV-associated Oropharynx Cancer, were posted on ClinicalTrials.gov on 2025-12-15. The study determined the maximally tolerated dose/fractionation to be 46.5 Gy × 15 fractions.
Background
Head and neck cancers encompass a range of malignancies, with oropharyngeal cancer being a significant subtype. A growing proportion of oropharyngeal cancers are associated with human papillomavirus (HPV) infection, which typically confers a more favorable prognosis compared to HPV-negative cases. Despite this, standard treatment regimens, often involving radiation therapy with concurrent chemotherapy, can lead to substantial acute and late toxicities, impacting patients' quality of life. There is an ongoing effort to de-intensify treatment for favorable-risk HPV-associated oropharyngeal cancer to reduce these side effects while maintaining high rates of disease control. Hypofractionated radiation therapy, which delivers a higher dose per fraction over a shorter overall treatment time, is one approach being explored for de-intensification.
Trial design
This completed Phase 1, single-arm study, titled "HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer," enrolled 24 participants. The trial focused on patients with Human Papillomavirus-Related Carcinoma and Oropharyngeal Cancer. The primary objective was to evaluate the tolerability and determine the maximally tolerated dose (MTD) of a de-intensified hypofractionated radiation therapy regimen, completed in 3 weeks (with an equivalent biologically effective dose to 60 Gy in 30 fractions), administered with concurrent weekly cisplatin.
Key results
The trial's key findings centered on determining the maximally tolerated dose and observing acute toxicities:
- The maximally tolerated dose/fractionation of hypofractionated radiation therapy was estimated to be 46.5 Gy × 15 fractions. This estimation was based on the incidence of dose-limiting toxicities observed during the dose-escalation phase.
- Clinician-reported acute toxicities were observed in multiple participants, with counts including: 18 participants, 15 participants, 13 participants, 11 participants, 9 participants, 7 participants, 2 participants, 1 participant, 5 participants, 2 participants, and 2 participants.
What this means
The determination of a maximally tolerated dose of 46.5 Gy × 15 fractions for de-intensified hypofractionated radiation therapy with concurrent weekly cisplatin represents a crucial step for patients with favorable HPV-associated oropharyngeal cancer. This Phase 1 finding provides a potential dose and schedule for further investigation in larger trials, aiming to reduce the overall treatment burden and associated toxicities compared to conventional regimens, while maintaining therapeutic efficacy. The observed acute toxicities will inform future safety protocols and patient management strategies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04580446, titled "HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer", were posted on 2025-12-15 on clinicaltrials.gov.