E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oropharyngeal cancer |
Oropharynxkarzinome |
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E.1.1.1 | Medical condition in easily understood language |
Throat cancer |
Kopf-Hals-Tumoren |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031096 |
E.1.2 | Term | Oropharyngeal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of the PATHOS study is to assess whether swallowing function can be improved following transoral resection of HPV-positive Oropharyngeal cancer (OPSCC), by reducing the intensity of adjuvant (postoperative) treatment protocols, either by giving a lower dose of radiotherapy or by giving radiotherapy without chemotherapy.
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Ziel der Studie ist es, festzustellen, ob eine Verringerung der Intensität der adjuvanten Behandlung, entweder durch eine Reduktion der Dosis der Strahlentherapie oder durch den Wegfall der Chemotherapie, zu einer besseren langfristigen Schluckfunktion führt. |
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E.2.2 | Secondary objectives of the trial |
Swallowing panel including qualitative and quantitative swallowing assessments Quality of life Acute and late toxicity Disease Free Survival Locoregional control Distant Metastases |
Schluckuntersuchungen für qualitative und quantitative Schluckbewertungen Lebensqualität Akut- und Spättoxizität krankheitsfreies Überleben lokoregionale Kontrolle Fernmetastasen |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed or suspected squamous cell carcinoma of the oropharynx. • UICC/AJCC TNM 7th edition stage T1-T3, N0-N2b (or UICC TNM 8th edition stage T1-T3, N0-N1) disease. [Staging should be based on cross sectional imaging investigations carried out within 10 weeks of study entry]. • Multidisciplinary team (MDT) decision to treat with primary transoral resection and neck dissection. • Patients considered fit for surgery and adjuvant treatment by the local MDT. • Aged 18 or over. • Written informed consent provided.
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• Histologisch bestätigtes oder vermutetes Plattenepithelkarzinom des Oropharynx • Erkrankung gemäß UICC/AJCC TNM 7th edition stage T1-T3, N0-N2b (oder UICC TNM 8th edition stage T1-T3, N0-N1). [Staging basierend auf bildgebenden Querschnittsuntersuchungen durchgeführt innerhalb von 10 Wochen nach Studienbeginn]. • Entscheidung von lokalen Teams, dass der Patient sich einer Operation unterziehen müsse, um den primären Tumor und Halslymphknoten zu entfernen. • Patienten, deren Gesundheitszustand eine Durchführung der geplanten Operation und der adjuvanten Radiotherapie zulässt • Alter ≥ 18 Jahren • Unterschriebene Einwilligungserklärung
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E.4 | Principal exclusion criteria |
• HPV negative squamous cell carcinomas of the head and neck. • T4 and/or T1-T3 tumours where transoral surgery is considered not feasible. • UICC/AJCC TNM 7th edition N2c-N3 nodal disease (or UICC/AJCC TNM 8th edition N2-N3 nodal disease). • Patients for whom transoral surgery and neck dissection is not considered the primary treatment modality. • Current smokers with N2b disease (including smokers up to 6 months before diagnosis), even if HPV-positive. Vaping is permitted and should be considered as non-smoking status. • Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction prior to index oropharyngeal cancer. • Distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g. CT thorax and upper abdomen or PET CT. • History of malignancy in the last 5 years, except basal cell carcinoma of the skin or carcinoma in situ of the cervix. • Women who are pregnant or breastfeeding and fertile women who will not be using contraception during the trial. |
• HPV-negative Plattenepithelkarzinome des Kopf-Hals-Bereichs • T4 und/oder T1-T3 Tumore, bei denen eine transorale Chirurgie als nicht durchführbar angesehen wird. • Lymphknotenstatus N2c-N3 gemäß UICC/AJCC TNM 7th edition N2c-N3 (oder N2-N3 gemäß UICC/AJCC TNM 8th Edition) • Patienten für welche eine transorale Chirurgie und Neck Dissection nicht als primäre Behandlungsmethode angesehen wird. • Aktive Raucher mit N2b Erkrankung (inbegriffen sind Patienten, die bis zu 6 Monaten vor Diagnose geraucht haben), auch wenn sie HPV-positiv sind. Dampfen (elektronische Zigaretten) ist gestattet und gilt als Nichtrauchen. • Jegliche bereits vorhandene medizinische Einschränkung, die die Schluckfunktion beeinträchtigt und / oder eine Schluckstörung, die vor der Diagnose des oropharyngealer Krebses vorangegangen war. • Fernmetastasen, die bei dem routinemäßigem pre-operativem Staging, z.B. CT Thorax und oberes Abdomen oder PET-CT, festgestellt werden. • Andere Malignome in den letzten 5 Jahren, außer kurativ Basaliom der Haut oder in situ Zervixkarzinom • Schwangere oder stillende Frauen und Frauen im gebärfähigen Alter ohne hochwirksame Empfängnisverhütung
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints of the PATHOS study are swallowing function as measured by the MD Anderson Dysphagia Inventory (MDADI), 12 months after treatment and overall survival.
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Die primären Endpunkte der PATHOS-Studie sind die Schluckfunktion, gemessen mit dem MD Anderson Dysphagia Inventory (MDADI), 12 Monate nach der Behandlung und das Gesamtüberleben. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Twelve months was chosen as the primary endpoint to evaluate long-term swallowing outcomes because longitudinal data show that functional recovery occurs primarily within 12 months, with little change in swallowing outcomes from 12 to 24 months. |
Der Zeitpunkt zwölf Monate wurden für den primären Endpunkt gewählt, um langfristige Schluckergebnisse zu bewerten, da Längsschnittdaten zeigen, dass die funktionelle Erholung vor allem innerhalb von 12 Monaten erfolgt, wobei sich die Schluckergebnisse von 12 bis 24 Monaten kaum ändern. |
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E.5.2 | Secondary end point(s) |
The secondary end-points are: • Swallowing panel measurements including qualitative and quantitative swallowing assessments. • Quality of Life (using EORTC QLQ C30 and HN35 questionnaires. • Acute and late toxicity measured using CTCAE V4.03 scoring criteria. • Disease free survival, locoregional control, distant metastasis
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Sekundäre Endpunkte sind: • Schluckpanelmessungen einschließlich qualitativer und quantitativer Schluckbewertungen • QOL (EORTC QLQ C30 und HN35) • Akut- und Spättoxizität (CTCAE v4.03) • krankheitsfreies Überleben, • Lokoregionale Kontrolle und Fernmetastasen. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will continue clinical follow-up for at least 5 years as per standard of care.
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Patients will continue clinical follow-up for at least 5 years as per standard of care.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Radiotherapie |
radiotherapy |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the date of final data capture to meet the trial endpoints. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 11 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |