Adaptative Radiotherapy to Decrease Xerostomia in Oropharynx Carcinoma

Study Overview
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Brief Summary
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The Phase III study will include 174 patients with locally advanced oropharynx carcinoma, receiving all arc-IMRT (Intensity-Modulated Radiation Therapy) (70 Gy) with concomitant systemic therapy. Two arc-IMRT treatment arms will be compared: one standard arm based on the use of a single pre-treatment planning and one experimental arm (adaptive RT) based on a weekly replanning to spare the salivary glands. The main objective is to increase by 25% the salivary flow (Parafilm) 12 months after RT thanks to adaptive RT, while not decreasing local control. The secondary objectives are to increase the salivary flow (scintigraphy), reduce xerostomia, acute and late toxicities (Eisbruch questionnaire, MDAS-HN, v.4 CTCAE), while maintaining local control (stopping rule of the trial if difference>15%). 174 patients will be included in 6 French centers for 2 years and followed for 2 years. The HPV (Human Papillomavirus) status will be identified and the tumors frozen. A central IMRT QA (Quality Assurance) will be performed.

Official Title
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Phase III Trial Testing the Benefit of Intensity-modulated Radiotherapy With Weekly Replanifications Versus Intensity Modulated Radiotherapy With Only One Planification in Locally Advanced Oropharynx Carcinoma for Decreasing Xerostomia

Conditions
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Oropharynx Cancer

Intervention / Treatment
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* Radiation: adaptative radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced non-metastatic carcinoma of the oropharynx limited to T3 and T4 (whatever the N) and N2-N3 (whatever the T)(AJCC stage III-IV) Age ≥ 18 years and ≤ 75 years Performance status (WHO ≤ 2) Renal, hepatic and cardiovascular functions allowing systemic treatment administration Adapted stomatologic care Signed informed consent form Membership or beneficiary of a national insurance scheme Exclusion Criteria: Both parotids totally included in the target volume Stages T1 or T2 with positive node disease N1 Neoadjuvant chemotherapy Exereses of primitive tumor and/or nodes History of other cancer within 5 years (except for basocellular epithelioma and cervical) Previous neck radiotherapy Platinum salts, 5FluoroUracile (5FU) agents or cetuximab chemotherapy considerations Unstable diseases (cardiovascular, renal, pulmonary, systemic lupus or sclerodermia)incompatible with study participation Patient participating in other therapeutic trial with experimental drug, 30 days before the inclusion. Patient already recruited in another biomedical research ( non interventional study is authorized) Pregnant or breast feeding patients Patient deprived of liberty, under tutorship, guardianship or placed under judicial protection Patient is deemed incapable of giving informed consent Patients who, for family, social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard radiotherapy<br>single pre-treatment planning before radiotherapy | |
| Experimental: adaptative radiotherapy<br>adaptive Radiotherapy based on a weekly replanning | Radiation: adaptative radiotherapy<br>* weekly replanning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary flow measure | The salivary flow is measured after stimulation with Parafilm at the time of inclusion and then 12 months after the end of radiotherapy. | 12 months after the end of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Xerostomia | salivary flow measured after stimulation before treatment, 6months, 18 months and 24 months after the end of radiotherapy Eisbruch's questionnaire before treatment, at 3, 6, 12, 18 and 24 months after the end of radiotherapy | From before treatment to 24 months after the end of radiotherapy | 
| Salivary flow | measured by scintigraphy | Before treatment and 12 months after the end of radiotherapy | 
| Local control | analysed according stages T and N, HPV status | 2 years | 
| Early and late toxicities | early toxicity : weekly assessment during radiotherapy until 3 months after the end late toxicity : 6, 12, 18 and 24 months after the end of radiotherapy | From beginning of the radiotherapy up to 2 years after the end of radiotherapy | 
| Survival | overall and disease free survival | 2 years | 
| Head and Neck functionality | MDASI-HN questionnaire before treatment, 3, 6, 12, 18 and 24 months after the end of radiotherapy | Before treatment to 24 months after the end of radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adaptative radiotherapy, oropharynx carcinoma, xerostomia