Feasibility of Patient Selection and Treatment of Head-neck Cancer With Proton Therapy in Denmark

Study Overview
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Brief Summary
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A study to investigate feasibility of local selection of patients with squamous cell carcinoma of the pharynx or larynx using anticipated benefit of proton radiotherapy in reducing the risk of late dysphagia or xerostomia.

Detailed Description
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In preparation for a randomised study in Denmark (DAHANCA 35) the feasibility of selecting newly diagnosed patients with squamous cell carcinoma of the pharynx or larynx for proton therapy at the local treatment centers is investigated. A proton and a photon doseplan is prepared for patients planned for primary radiotherapy . If proton radiotherapy reduces the anticipated absolute risk of dysphagia >= grade 2 (DAHANCA scale and/or xerostomia >= grade 2 (EORTC Head-Neck 35) with a clinical relevant value the patient is offered proton therapy at the Danish Center for Particle Therapy. The anticipated risk of xerostomia and dysphagia is estimated using Normal-Tissue Complication Models (NTCP). At least five patients from each of the six Danish centers are required in this feasibility study.

Official Title
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DAHANCA Proton Feasibility Study

Conditions
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Head-and-neck Cancer

Intervention / Treatment
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* Other: Proton radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven squamous cell carcinoma of the pharynx or larynx planned for primary radiotherapy with curative intent A predicted clinical significant reduction in the risk of any of the two primary endpoints (>= grade 2 observer-rated dysphagia or grade 2 patient-reported xerostomia) after proton therapy compared to photon therapy based on comparison of the individual patient dose plans No current or earlier malignancies, which may influence treatment, evaluation or outcome of the head-neck cancer Informed consent as required by law Above 18 years of age Exclusion Criteria: Patient with cancers of the glottic larynx (stage I/II), skull base, sino-nasal area, nasopharynx, unknown primary tumor and prior malignancies. Patients with contraindications for proton therapy (as per 2019 pacemakers, implanted defibrillators and tracheostomy) Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic Distant metastasis Previous radiotherapy of the head and neck Previous surgery for the primary cancer with curative intent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single group feasibility study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton radiotherapy<br>Proton radiotherapy according to the guidelines defined by the Danish Head-Neck Cancer Group (DAHANCA). Treatment: 66-68 Gy/ 33-34 fx/ 6/W,with cisplatin 40 mg/m2/W and nimorazole to suitable patients | Other: Proton radiotherapy<br>* Proton radiotherapy according to the guidelines defined by the Danish Head-Neck Cancer Group (DAHANCA). Treatment: 66-68 Gy/ 33-34 fx/ 6/W, with cisplatin 40 mg/m2/W and nimorazole to suitable patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dysphagia >= grade 2 | The rate of observer-reported dysphagia >= grade 2 measured by the DAHANCA late toxicity score (grade 0-4, with 0 being best) | Six months after end of radiotherapy | 
| Xerostomia = grade 2 | The rate of patient-reported xerostomia measured by the EORTC Quality of life questionnaire (QLQ) Head-Neck (HN) 35 (grade 1-4, with 1 being best) | Six months after end of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loco-regional tumor control | Time to event of local-regional failure, from date of randomization to the date of first documented loco-regional failure. Rates are estimated by the Kaplan-Meier method. Interim analyses after 100, 200 and 300 patients. Will not be reported before the primary endpoint. | Up to five years after end of radiotherapy | 
| Overall survival | From date of randomisation to date of death | Up to five years after end of radiotherapy] | 
| Acute toxicity | DAHANCA acute toxicity score (grade 0-4, 0 being best) | From the beginning of and up to two months after end of radiotherapy] | 
| Late toxicity | DAHANCA late toxicity score (grade 0-4, 0 being best) | From two months to five years after end of radiotherapy] | 
| EORTC QLQ-Head-Neck 35 | Swallowing and social-eating scale and specific HN35 items related to eating and pain (grade 1-4, 1 being best) | Up to five years after end of radiotherapy | 
| EORTC C30 | Specific C30 items related to fatigue, nausea and vomiting (grade 1-4, 1 being best) | Up to five years after end of radiotherapy] | 
| Time from referral to treatment | Time from referral to proton center to first proton treatment | From date of referral to proton treatment to first proton treatment (Assessed up to 60 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proton radiotherapy