DAHANCA 37. Re-irradiation With Proton Radiotherapy

Study Overview
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Brief Summary
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Summary Design Phase II observational Treatment 60 Gy/50 fx / 10W-1 at 1.2 Gy/fx o i.e. EQD2 tumor=56 Gy, EQD2 late=50.4 Gy at α/β= 10 and 3, respectively Proton radiotherapy Concomitant cisplatin for eligible patients* Nimorazole recommended for SCC* *The concurrent medical treatment (weekly cisplatin and nimorazole) are prescribed according to the national treatment guidelines, and are not part of the experimental treatment. Endpoints Primary: o Any new late toxicity grade >=3 according to CTC AE 5.0 Secondary Side effects according to DAHANCA scoring system Quality of life and PROM according to EORTC C30 and HN43 Loco-regional control (LRC) Overall survival (OS)

Detailed Description
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Summary Design Phase II observational Inclusion criteria Histological verified loco-regional recurrence or new primary Available dose plan from primary radiotherapy course Comparative dose plan with advantages for proton radiotherapy e.g. integral dose Dmax dose (0.03 cm3) on the cumulated photon dose plan≥90 Gy Complete Response (CR)* after initial therapy, except in the case where the recurrence is considered a geometric miss (recurrence center of mass (COM) outside the 95% of prescription dose. Inoperable or salvage surgery with R1/R2 resection, extranodal extension (ENE) or extensive soft tissue infiltration Absence of distant metastasis at both clinical examination AND PET-CT or CT of thorax and upper abdomen Life expectancy due to age and co-morbidity of >=1 year. The general condition must be sufficient to tolerate persistent significant side effects, e.g. tube or cannulae PS<=2 (WHO See appendix) The patients should be able to read Danish in order to participate with quality of life questionnaires, but can participate in the rest of the protocol without being fluent in Danish, if capable of reading the patient information. * Complete Response is defined as the situation when a trained clinician, ideally at a multidisciplinary team conference, defines the patient as in complete remission, based on clinical examination and available imaging. This status can of course later be considered wrong as new information becomes available (sub-centimeter nodes grow etc.) Exclusion criteria Radical surgery (R0) and absence of adverse prognostic pathological features Lymphoma or malignant melanoma Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic As of 2019, patients with tracheal cannulas are excluded due to dose uncertainties. This may change if a technical solution becomes available. Treatment 60 Gy/50 fx / 10W-1 at 1.2 Gy/fx o i.e. EQD2 tumor=56 Gy, EQD2 late=50.4 Gy at α/β= 10 and 3, respectively Proton radiotherapy Concomitant cisplatin for eligible patients* Nimorazole recommended for SCC* *The concurrent medical treatment (weekly cisplatin and nimorazole) are prescribed according to the national treatment guidelines, and are not part of the experimental treatment. Endpoints Primary: o Any new late toxicity grade >=3 according to CTC AE 5.0 Secondary Side effects according to DAHANCA scoring system Quality of life and PROM according to EORTC C30 and HN43 Loco-regional control (LRC) Overall survival (OS) Derived projects Morbidity (NTCP) modeling for cumulative doses Metrics for uncertainties regarding cumulative doses

Official Title
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DAHANCA 37 A Phase II Study of Intensity Modulated Proton Therapy (IMPT) for Re-irradiation With Curative Intent for Recurrent or New Primary Head and Neck Cancer

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Radiation: Re-irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological verified loco-regional recurrence or new primary Available dose plan from primary radiotherapy course Comparative dose plan with advantages for proton radiotherapy e.g. integral dose Dmax dose (0.03 cm3) on the cumulated photon dose plan≥90 Gy Complete Response (CR)* after initial therapy, except in the case where the recurrence is considered a geometric miss (recurrence center of mass (COM) outside the 95% of prescription dose. Inoperable or salvage surgery with R1/R2 resection, extranodal extension (ENE) or extensive soft tissue infiltration Absence of distant metastasis at both clinical examination AND PET-CT or CT of thorax and upper abdomen Life expectancy due to age and co-morbidity of >=1 year. The general condition must be sufficient to tolerate persistent significant side effects, e.g. tube or cannulae PS<=2 (WHO See appendix) Exclusion Criteria: Radical surgery (R0) and absence of adverse prognostic pathological features Lymphoma or malignant melanoma Inability to attend full course of radiotherapy or follow-up visits in the outpatient clinic As of 2019, patients with tracheal cannulas are excluded due to dose uncertainties. This may change if a technical solution becomes available.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Re-Irradiation with protons<br>60 Gy in 50 fraktions, 10 weekly with protons | Radiation: Re-irradiation<br>* Cisplatin for all eligible patients, nimorazole for all SCC<br>* Other names: nimorazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any new grade >=3 toxicity | CTC AE 5.0 | 3 years after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effects, any grade | According to CTC AE or Dahanca | 5 years after radiotherapy | 
| Quality of life and PROM | EORTC QLQ HN43 , swallowing scale. Difference (mean) between baseline and 6 months | 6 months | 
| Loco-regional control (LRC) | Abscence of locoregional failure | 5 years after radiotherapy -actuarial analysis | 
| Overall survival (OS) | Abscence of death | Median Survival up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent, reirradiation, second primary