E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
1. To demonstrate if swallowing function can be improved and toxicities reduced following transoral surgery for HPV-positive oropharyngeal cancer, by reducing the intensity of adjuvant treatment protocols.
2. To demonstrate the non-inferiority of reducing the intensity of adjuvant treatment protocols in terms of overall survival |
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E.2.2 | Secondary objectives of the trial |
1. Standardisation of transoral surgery for OPSCC by rigorous application of surgical standards.
2. The credentialing of participating surgeons.
3. Standardisation of surgical margin assessment after transoral surgery and examination of the clinical-pathological correlates of HPV-positive
OPSCC by central pathology review of specimens.
4. Development of a standardised, multi-faceted swallowing assessment tool for patients undergoing treatment for OPSCC, applicable by Speech
and Language Therapists (SLTs) in multiple centres.
5. Development of a RTTQA package and adjuvant Intensity Modulated Radiotherapy (IMRT) protocol for OPSCC. Dose/volume data for
swallowing structures will be recorded so that the relationship between long-term swallowing function (phase II endpoint) and dose/volumes
received by the swallowing organs can be prospectively analysed.
6. A programme of translational research will be developed to utilize PATHOS clinical samples. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Little is yet known about the biological mechanisms underlying the development of HPV positive oropharyngeal squamous cell carcinoma and its response to treatment. Further understanding will only be gained using high quality bioresources such as those we propose to collect from patients consented to undergo surgery as part of PATHOS.
The bioresource collection will underpin an integrated programme of research (PATHOS-TRANS) which will allow to gain, inter alia, insight into the prevalence and characteristics of viral integration events and viral gene expression, the nature of tumour based immune synapse interactions and their impact on outcome and how these interactions are influenced by intra-tumour heterogeneity. Moreover, PATHOS, PATHOS-T and PATHOS-TRANS affords us an ideal opportunity to identify putative blood-based biomarkers of tumour phenotype and disease behaviour. It is important to note that the rapid adoption of any research finding into clinical practice will be facilitated by our intention to collect all bioresources to Good Clinical Laboratory Practice (GCLP) standards. |
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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 radiotherapy.
- Aged 18 or over.
- Patients must be affiliated to a Social Security System.
- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their
written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
- Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures. |
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E.4 | Principal exclusion criteria |
- Known 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.
- Persons deprived of their liberty or under protective custody or guardianship.
- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival
swallowing function as measured by the MD Anderson Dysphagia
Inventory (MDADI) score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Swallowing panel measurements including qualitative and quantitative swallowing assessments
- QOL (using EORTC QLQ C30 and HN35 questionnaires).
- Acute and late toxicity, assessed using NCI CTCAE criteria version 4.03.
- Overall survival, disease free survival, locoregional control, distant metastases. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments take place at baseline (before surgery), 4 weeks post surgery and then at 1, 6, 12 and 24 months after adjuvant therapy |
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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 | Yes |
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 |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
France |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
Switzerland |
United Kingdom |
United States |
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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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |