At a glance
ClinicalIndex Comparison Record- ✓Age ≥18 years at informed consent
- ✓Squamous cell carcinoma of oropharynx, hypopharynx, or larynx proven by cytology/histology
- ✓Amenable for curative intent proton or photon therapy per model-based selection criteria
- ✓Radiotherapy with or without concurrent radiosensitizer
- ✕Prior irradiation to same target volume
- ✕Chronic inflammatory disease or immune disorders that may disturb translational immune read-out
- ✕Current treatment for other malignant disease or treated within last 2 years (except in situ or basal cell carcinoma of skin)
- ✕Psychological, familial, sociological, or geographical conditions impacting protocol compliance
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
NCT05364411N/ARecruitingUpdate OverdueUpdated 28mo ago · Completion was 13mo agoHYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons to Combat Radiation-induced Immunosuppression in Head and Neck Squamous Cell Carcinoma (HYDRA)
In Brief
A clinical study evaluating HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA) and conventional fractionated radiotherapy for Head and Neck Squamous Cell Carcinoma and 4 related conditions. Currently recruiting, targeting 100 participants across 1 site.
Signals
Detailed Summary
Radiotherapy for advanced-stage head and neck squamous cell carcinoma (HNSCC) results in an unfavorable 5-year overall survival of 40%, and there is a strong biological rationale for improving outcome by combinatorial treatment with immunotherapy. However, also immunosuppressive effects of radiotherapy have been reported and recently a randomized phase-III trial failed to show any survival benefit following the combination of a PD-L1 inhibitor with chemoradiotherapy. The hypothesis is that the combination of these individually effective treatments failed because of radiation-induced lymphodepletion and that the key therefore lies in reforming conventional radiotherapy, which typically consists of large lymphotoxic radiation fields of 35 fractions. By integrating modern radiobiology and individually established innovative radiotherapy concepts, the patient's immune system could be maximally retained. This will be achieved by 1) increasing the radiation dose per fraction so that the total number of fractions can be reduced (HYpofractionation), 2) by redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective-field dose (Dose-redistribution) and 3) by using RAdiotherapy with protons instead of photons (HYDRA). The objectives of this study are to determine the safety of HYDRA with protons and photons by conducting two parallel phase-I trials. HYDRA's efficacy will be compared to standard of care (SOC). The immune effects of HYDRA-protons will be evaluated by longitudinal immune profiling and compared to HYDRA-photons and SOC (with protons and photons). There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated-immunotherapy combination trials. This trial therefore is an important step towards future personalized immuno-radiotherapy combinations with the ultimate goal to improve survival for patients with HNSCC.
Study Details
Timeline
Interventions
20 daily fractions, 5 times per week
35 daily fractions, 5 times per week