An interventional study of HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA) and conventional fractionated radiotherapy in Head and Neck Squamous Cell Carcinoma, Hypofractionation and Radiotherapy, sponsored by Joris B.W. Elbers. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-20.
Sponsored by Joris B.W. Elbers · Not applicable, Interventional, and Treatment
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.
The HYDRA dose prescriptions are, in 20 fractions (instead of the conventional 35 fractions):
Patients who receive the HYDRA intervention treatment, as well as patients who receive standard of care may require the addition of a concurrent radiosensitizer based on clinicopathological features according to standard of care. Currently, the only two registered radiosensitizers are platinum-based chemotherapy (cisplatin/carboplatin) and cetuximab. These radiosensitizers should be administered according to standard care treatment protocols.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's planned enrollment of 100 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →This is the only study on the registry with Joris B.W. Elbers as lead sponsor.
Counted across the registry records on this site, refreshed daily.
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
Written informed consent obtained.
Exclusion criteria
Patients who do not meet the inclusion criteria as specified in paragraph 4.2, and/or who meet the following additional criteria:
group 1, n=25, run at HollandPTC
Radiation: HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA)
group 2, n=25, run at HollandPTC
Radiation: conventional fractionated radiotherapy
group 3, n=25 run at Erasmus MC
Radiation: HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA)
group 4, n=25 run at Erasmus MC
Radiation: conventional fractionated radiotherapy
20 daily fractions, 5 times per week
35 daily fractions, 5 times per week
Safety of HYDRA-protons and HYDRA-photons in terms of radiation-induced grade 3-4 late toxicity, physician-reported by CTCAE v5.0, monitored until 1 year after the last patient has completed HYDRA.
HYDRA is randomized with standard of care for translational research purposes; a direct comparison of toxicity will statistically not be conclusive and is outside the scope of this study.
Time frame: month 1-36
Objective response after HYDRA defined by radiological response on CT-scans or MRI in comparison to standard of care
Objective response rate 3 months after HYDRA (group 1 and 3), defined by radiological response on CT-scans or MRI using RECIST version 1.1 and/or histopathological confirmation of residual disease, in comparison to standard of care (group 2 and 4, respectively), 3 months after end of treatment
Time frame: month 1-27
Efficacy of HYDRA in terms of in-field and nodal elective field tumor control at 1 year
Efficacy of HYDRA (group 1 and 3) in terms of in-field and nodal elective field tumor control, 1 year after the last patient is included, in comparison to group 2 and 4, respectively.
Time frame: month 24-36
Immune profile (changes) between all 4 treatment groups
Numbers and phenotype of peripheral immune cell populations in blood at baseline, related to patient- and tumor characteristics, and differences between temporal changes of these immune markers during/after treatment at 6 timepoints in group 1-4.
Time frame: month 1-27
Plan to share: No — tba
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