HYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons in HNSCC

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.

Conditions

• Head and Neck Squamous Cell Carcinoma
• Hypofractionation
• Radiotherapy
• Proton Therapy
• Immune System Suppression

Interventions

RADIATION

HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA)

20 daily fractions, 5 times per week

RADIATION

conventional fractionated radiotherapy

35 daily fractions, 5 times per week

Sponsors & Collaborators

• Erasmus Medical Center

  collaborator OTHER

• HollandPTC

  collaborator INDUSTRY

• Joris B.W. Elbers

  lead OTHER

Principal Investigators

• Joris BW Elbers, MD, PhD · Erasmus MC, Rotterdam / HollandPTC, Delft - The Netherlands

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-10-10

Primary Completion

2025-06-01

Completion

2026-06-01

Countries

• Netherlands

Study Locations