Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS) (PATHOS)
Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer
About this trial
This is an interventional treatment trial for Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer focused on measuring Human papillomavirus HPV positive oropharyngeal cancer
Eligibility Criteria
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.
- 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.
- Written informed consent provided.
Exclusion Criteria:
- Known HPV negative squamous cell carcinomas of the head and neck: A negative result for p16 Immunohistochemistry automatically excludes a patient from the trial. If initial p16 testing is positive but High Risk HPV (HR HPV) In-Situ Hybridization (ISH)/Polymerase Chain Reaction (PCR) does not demonstrate the presence of HR HPV DNA, the patient will also be excluded. Patients who are p16+ may complete swallowing assessments, excluding videofluoroscopy, and surgery whilst HR HPV DNA status is being determined (with recourse to central concordance testing, if appropriate, for UK centres). HPV positivity, as determined by p16 and the demonstration of HR HPV DNA is essential before patients undergo videofluoroscopy or randomisation.
- 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 clinically staged 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.
- Patients with distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g., CT thorax and upper abdomen or PET-CT.
- Patients with a 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.
Sites / Locations
- Board of Trustees of the Leland Stanford Junior UniversityRecruiting
- Advent HealthRecruiting
- MD Anderson Cancer Centre
- Metro South HealthRecruiting
- UnicancerRecruiting
- Vivantes KlinikumRecruiting
- Asklepios KlinikenRecruiting
- Universitat LeipzigRecruiting
- Ernst von Bergmann KlinikumRecruiting
- Städtisches Klinikum SolingenRecruiting
- Universitätsklinikum UlmRecruiting
- University Hospitals Dorset NHS FoundationRecruiting
- Royal United Hospitals Bath NHS Foundation TrustRecruiting
- Queen Elizabeth HospitalRecruiting
- Royal Blackburn HospitalRecruiting
- Royal Sussex County HospitalRecruiting
- University Hospitals Bristol NHS Foundation TrustRecruiting
- Cambridge University Hospitals NHS Foundation TrustRecruiting
- Kent and Canterbury HospitalRecruiting
- HPV Research Group Section of Pathology Cardiff University ,School of Medicine
- Cardiff and Vale University Local Health BoardRecruiting
- Centre for Trials Research
- Velindre NHS TrustRecruiting
- Castle Hill HospitalRecruiting
- Derby Teaching Hospitals NHS Foundation TrustRecruiting
- Western General HospitalRecruiting
- Royal Devon University Health Care NHS Foundation TrustRecruiting
- Royal Surrey County HospitalRecruiting
- St James University HospitalRecruiting
- Liverpool Head and Neck CentreRecruiting
- University of Liverpool
- Cwm Taf Bro MorganwgRecruiting
- University College London Hospitals NHS Foundation TrustRecruiting
- Guys and St Thomas's NHS Foundation TrustRecruiting
- St Georges University HospitalRecruiting
- Imperial College Healthcare NHS TrustRecruiting
- Central Manchester University Hospital NHS Foundation TrustRecruiting
- The Christie NHS Foundation TrustRecruiting
- The Pennine Acute Hospital TrustRecruiting
- The James Cook University HospitalRecruiting
- Royal Victoria Infirmary
- Newcastle upon Tyne Hospitals NHS Foundation TrustRecruiting
- Aneurin Bevan University Health BoardRecruiting
- Nottingham City HospitalRecruiting
- Oxford University Hospitals NHS Foundation TrustRecruiting
- University Hospital PlymouthRecruiting
- Queen Alexandra HospitalRecruiting
- Royal Preston HospitalRecruiting
- Royal Berkshire HospitalRecruiting
- University Hospital SouthamptonRecruiting
- City Hospitals Sunderland NHS Foundation TrustRecruiting
- Swansea Bay University Local Health BoardRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
No Intervention
Active Comparator
Experimental
Active Comparator
Experimental
A: No adjuvant treatment
B1: Postoperative radiotherapy 60 Gray
B2: Postoperative radiotherapy 50 Gray
C1: Postoperative radiotherapy 60 Gray with Cisplatin
C2: Postoperative radiotherapy 60 Gray without chemotherapy
Group A Patients with tumours which exhibit no adverse histological features. Patients in this group will not receive any adjuvant treatment as per standard of care.
Arm B1: postoperative radiotherapy (PORT) at a dose of 60 Gray (Gy) in 30 fractions over 6 weeks. Group B: Patients with: T3 tumours (or T1-T2 tumours with additional risk factors), TNM 7th edition pN2a (metastasis in single ipsilateral node 31-60 mm diameter) or pN2b (metastasis in multiple ipsilateral nodes <61 mm diameter) disease, tumours with evidence of perineural and/or vascular invasion, and/or a histologically normal tissue margin around the primary tumour of 1-5mm and, in the case of TLM, marginal biopsies free of tumour.
Arm B2: Postoperative radiotherapy (PORT) at a dose 50 Gray in 25 fractions over 5 weeks. Group B: Patients with: T3 tumours (or T1-T2 tumours with additional risk factors), TNM 7th edition pN2a (metastasis in single ipsilateral node 31-60 mm diameter) or pN2b (metastasis in multiple ipsilateral nodes <61 mm diameter) disease, tumours with evidence of perineural and/or vascular invasion, and/or a histologically normal tissue margin around the primary tumour of 1-5mm and, in the case of TLM, marginal biopsies free of tumour.
Arm C1: postoperative radiotherapy at a dose of 60 Gray in 30 fractions over 6 weeks with concurrent Cisplatin chemotherapy (POCRT). Cisplatin may be given 3 weekly (100mg/m2 week 1 and week 4 of radiotherapy) or weekly (40mg/m2 weekly during radiotherapy), according to local practice. Group C: Patients with tumours of any T or any N stage, which exhibit the following high risk pathological features will be included: A histologically normal tissue margin around the primary tumour of <1mm and, in the case of TLM, marginal biopsies free of tumour and /or extracapsular spread (ECS) of nodal disease
Arm C2: Postoperative radiotherapy at a dose of 60 Gray in 30 fractions over 6 weeks without chemotherapy (Test Arm C2). Group C: Patients with tumours of any T or any N stage, which exhibit the following high risk pathological features will be included: A histologically normal tissue margin around the primary tumour of <1mm and, in the case of TLM, marginal biopsies free of tumour and /or extracapsular spread (ECS) of nodal disease