E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
squamous cell carcinoma of the oropharynx |
Plattenepithelkarzinom des Oropharynx |
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E.1.1.1 | Medical condition in easily understood language |
malignant tumor of the oropharynx |
bösartiger Tumor des Mundrachenraums |
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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 | LLT |
E.1.2 | Classification code | 10026184 |
E.1.2 | Term | Malignant neoplasm of oropharynx |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To evaluate the effectiveness of primary surgical versus non-surgical treatment of locally advanced, but transorally resectable oropharyngeal cancer in terms of time to local or locoregional failure or death from any cause (LRF) |
Bewertung der Effektivität von transoraler Kopf-Hals-Chirurgie versus nicht-operative Behandlung bei lokal fortgeschrittenen, aber transoral resektablen Oropharynxkarzinomen und Zeit bis zum lokalen und lokoregionären Therapieversagens. |
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E.2.2 | Secondary objectives of the trial |
Effectiveness of primary surgical versus non-surgical treatment of locally advanced, but transorally resectable oropharyngeal cancer with respect to • overall and disease-free survival of both treatments • acute toxicity and late morbidity (including swallowing function) until 3 years after randomization • Quality of life • Cost-effectiveness/ cost-utility analysis
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Effektivität von transoraler Kopf-Hals-Chirgurgie versus nicht-operative Behandlung bei lokal fortgeschrittenen, aber transoral resektablen Oropharynxkarzinomen in Bezug auf: • Gesamt-Überleben und krankheitsfreies Überleben in beiden Behandlungsarmen • Akute Toxizität und späte Morbidität (einschließlich Schluckfunktion) bis 3 Jahre nach Randomisierung • Lebensqualität • Kosten-Nutzwert-Analyse |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically proven SCC of the oropharynx; T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0, with only amendable to transoral resection) • Primary tumor must be resectable through transoral approach • p16 immunohistochemitry by local pathology or FFPE tissue must be available for central HPV diagnostic • Written and signed informed consent • Briefing through surgeon and radiation oncologist • ECOG PS ≤2, Karnofsky PS ≥ 60 % • Age ≥ 18 • Curative treatment intent • Adequate bone marrow function: leucocytes > 3.0 x 109/L, neutrophils > 1.5 x 109/L, platelets > 80 x 109/L, hemoglobin > 9.5 g/dL • Adequate liver function: Bilirubin < 2.0 g/dL, SGOT, SGPT, < 3 x ULN • If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing. • dental examination and appropriate dental therapy if needed prior to beginning of radiotherapy • Nutritional evaluation prior to initiation of therapy and optional prophylactic gastrostomy (PEG) tube placement
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E.4 | Principal exclusion criteria |
• Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix • Unknown primary (CUP), nasopharynx, hypopharynx, laryngeal or salivary gland cancer • Metastatic disease • Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C • Hemoglobin level <9.5g/dl within 4 weeks before randomization • Pregnancy or lactation • Women of child-bearing potential with unclear contraception • Previous treatment with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening • Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol • Patients institutionalized by official means or court order • Deficient dental preservation status or not accomplished wound healing
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to local or locoregional failure (LRF) (defined as time from randomization to local or locoregional failure or death from any cause, whatever occurs first) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
treatment phase: at every visit according to protocol follow-up: every three months until 36 month, every 6 months until end of study |
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E.5.2 | Secondary end point(s) |
• Overall and disease-free survival • Therapy-associated toxicity including swallowing function • QoL and QALY • Direct and indirect costs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
treatment phase: at every visit according to protocol follow-up: every three months until 36 month, every 6 months until end of study |
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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 |
surgery followed by adjuvant Radio(chemo)therapy versus primary Radiochemotherapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 20 |
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 | Yes |
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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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 | |
E.8.9.1 | In the Member State concerned days | |