Head and Neck Squamous Cell Carcinoma Clinical Trial
— HYDRAOfficial title:
HYpofractionated, Dose-redistributed RAdiotherapy With Protons and Photons to Combat Radiation-induced Immunosuppression in Head and Neck Squamous Cell Carcinoma (HYDRA)
NCT number | NCT05364411 |
Other study ID # | HYDRA |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | October 10, 2022 |
Est. completion date | June 1, 2026 |
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.
Status | Recruiting |
Enrollment | 100 |
Est. completion date | June 1, 2026 |
Est. primary completion date | June 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | In order to be eligible to participate in this study, a subject must meet all of the following criteria: - = 18 years old at time of signing informed consent. - WHO 0-2 - Squamous cell carcinoma of the oropharynx, hypopharynx and larynx* proven by cytology / histology - Patients amenable for curative intent proton therapy (by model-based selection criteria, according to the Dutch standard of care) or photon therapy. - Radiotherapy with or without concurrent radiosensitizer. - Ability to understand the requirements of the study and to give written informed consent, as determined by the treating physician. - Written informed consent obtained. - Note: The HYDRA dose prescriptions should be applicable for all HNSCC patients and should therefore ideally be tested within the full range of treatment indications, e.g. multiple tumor subsites and both chemoradiotherapy and radiotherapy alone. There are several reports about acceptable acute toxicity following hypofractionated chemoradiotherapy in advanced stage HNSCC. However, concerns about late toxicity remain, especially for laryngeal carcinoma. Patients with laryngeal carcinoma are therefore initially excluded, until these patients are also considered eligible for treatment with HYDRA. The statistical considerations and interim safety analyses for this purpose and the decision-making / consultation are further described elsewhere. Exclusion criteria Patients who do not meet the inclusion criteria as specified in paragraph 4.2, and/or who meet the following additional criteria: - 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. |
Country | Name | City | State |
---|---|---|---|
Netherlands | Erasmus MC | Rotterdam | Zuid Holland |
Lead Sponsor | Collaborator |
---|---|
Joris B.W. Elbers | Erasmus Medical Center, HollandPTC |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 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 | month 1-27 | |
Secondary | 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. | month 24-36 | |
Secondary | 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. | month 1-27 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05094804 -
A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
|
Phase 1/Phase 2 | |
Recruiting |
NCT03317327 -
REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors
|
Phase 1/Phase 2 | |
Terminated |
NCT02892201 -
Pembrolizumab in HNSCC With Residual Disease After Radiation
|
Phase 2 | |
Active, not recruiting |
NCT04854499 -
Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma
|
Phase 2 | |
Terminated |
NCT04110249 -
Photoacoustic Imaging for Measuring Tumors and Normal Tissue in Patients With Head and Neck Cancer
|
N/A | |
Terminated |
NCT02495896 -
Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05107674 -
A Study of NX-1607 in Adults With Advanced Malignancies
|
Phase 1 | |
Recruiting |
NCT05338905 -
Intensive Symptom Surveillance Guided by Machine Learning-Directed Risk Stratification in Patients With Non-Metastatic Head and Neck Cancer, The INSIGHT Trial
|
N/A | |
Recruiting |
NCT04045496 -
A First-in-Human, Phase 1 Study of JAB-3312 in Adult Patients With Advanced Solid Tumors
|
Phase 1 | |
Completed |
NCT04452214 -
A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04096638 -
Safety and Efficacy of SB 11285 Alone and in Combination With Atezolizumab in Patients With Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT03070366 -
Stereotactic Radiotherapy Combined With Chemotherapy or Not for Treatment of Oligometastases in HNSCC
|
Phase 2 | |
Not yet recruiting |
NCT06289049 -
Heavy Strength Training in Head and Neck Cancer Survivors
|
Phase 2 | |
Recruiting |
NCT02661152 -
DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC.
|
Phase 3 | |
Terminated |
NCT02488629 -
Study of SCB01A in Patient With Head and Neck Cancer
|
Phase 2 | |
Completed |
NCT01697800 -
A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract
|
Phase 2 | |
Completed |
NCT01427478 -
Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck
|
Phase 3 | |
Recruiting |
NCT05437380 -
Peritumoral Microbubbles and CEUS for SLN Detection and Biopsy in HNSCC
|
N/A | |
Recruiting |
NCT05065086 -
Single Modality Trans Oral Robotic Surgery for Primary Oropharyngeal Cancer: Exploring the Impact of Surgical Margins on Local Disease Recurrence
|
||
Completed |
NCT03022409 -
A Study to Investigate Biomarker Effects of Pre-Surgical Treatment With DNA Damage Repair (DDR) Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).
|
Phase 1 |