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

NCT05364411 | Recruiting DMC

• 1 other identifier: HYDRA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• 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.

  month 1-36

Secondary Outcomes (3)

• Objective response after HYDRA defined by radiological response on CT-scans or MRI in comparison to standard of care

  month 1-27

• Efficacy of HYDRA in terms of in-field and nodal elective field tumor control at 1 year

  month 24-36

• Immune profile (changes) between all 4 treatment groups

  month 1-27

Study Arms (4)

HYDRA-protons

EXPERIMENTAL

group 1, n=25, run at HollandPTC

Radiation: HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA)

Conventional fractionated proton therapy

ACTIVE COMPARATOR

group 2, n=25, run at HollandPTC

Radiation: conventional fractionated radiotherapy

HYDRA-photons

EXPERIMENTAL

group 3, n=25 run at Erasmus MC

Radiation: HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA)

Conventional fractionated photon therapy

ACTIVE COMPARATOR

group 4, n=25 run at Erasmus MC

Radiation: conventional fractionated radiotherapy

Interventions

HYpofractionated, Dose-redistributed RAdiotherapy (HYDRA) RADIATION

20 daily fractions, 5 times per week

HYDRA-photons; HYDRA-protons

conventional fractionated radiotherapy RADIATION

35 daily fractions, 5 times per week

Conventional fractionated photon therapy; Conventional fractionated proton therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Previously treated by irradiation on the same target volume
• Chronic inflammatory disease or immune disorders which, according to the principal investigator, may disturb the translational immune-read out.
• Patients currently under treatment for other malignant disease (unless in situ carcinoma or basal cell carcinoma of the skin), or treated for other malignant disease within the last 2 years.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule in the participating hospitals.
• Any other serious medical condition that could interfere with follow-up.

Sponsors & Collaborators

• Joris B.W. Elbers: lead
• Erasmus Medical Center: collaborator
• HollandPTC: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3015 GL, Netherlands

RECRUITING

Related Publications (1)

• Elbers JBW, Gunsch PA, Debets R, Keereweer S, van Meerten E, Zindler J, van Norden Y, Hoogeman MS, Verduijn GM, Kroesen M, Nout RA. HYpofractionated, dose-redistributed RAdiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma: study protocol of the phase I HYDRA trial. BMC Cancer. 2023 Jun 13;23(1):541. doi: 10.1186/s12885-023-11031-w.

  PMID: 37312053 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Joris BW Elbers, MD, PhD

  Erasmus MC, Rotterdam / HollandPTC, Delft - The Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joris BW Elbers, MD, PhD

CONTACT

0031207041249; j.elbers@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Model Details: Two parallel, non-comparative phase-I trials of HYDRA-protons run at HollandPTC (group 1, n=25) and HYDRA-photons (group 3, n=25) run at the Erasmus MC. Toxicity will be monitored until 1 year after the last patient has completed HYDRA. This will result in a median follow-up of approximately 2 years. Patients will subsequently receive follow-up according to standard of care up to 5 years after treatment for the evaluation of very late-onset toxicity. For translational immune profiling, HYDRA-protons and HYDRA-photons will be randomized by minimization (1:1 ratio) against SOC: conventional fractionated proton therapy in HPTC (group 2, n=25) and conventional fractionated photon therapy in the Erasmus MC (group 4, n=25), respectively.

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 6, 2022
• Study Start: October 10, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)