Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS)

What this trial studies

PATHOS is a multicentre, open-label, parallel-group Phase II/III randomised controlled trial (RCT). The phase II target of 242 patients was reached in December 2018 and there was a seamless transition into Phase III. The protocol was amended in September 2018 to incorporate the changes associated with the phase III transition. The amendment included changes to the outcome measures and sample size calculations. In March 2024, a protocol amendment increasing the target recruitment to Phase III of the study from 1100 to 1269 patients was approved. Patients eligible for the study must have biopsy proven oropharyngeal squamous cell carcinoma (OPSCC) clinically staged T1T3 N0N2b. Their primary tumour, as judged by the local MDT, must be considered resectable via a transoral approach. Having secured informed consent, patients with centrally or locally determined HPV positive tumours will undergo baseline assessment of swallowing function (includes; MDADI score, videofluoroscopy, PSSH\& N, 100 mL water swallow test) and complete QOL questions (EORTC QLQC30 and EORTC QLQH\&N35) prior to surgery. Transoral Laser Microsurgery, Transoral Robotic Surgery \& Endoscopically assisted Transoral Surgery are all accepted transoral techniques for the study. A lateral oropharyngectomy performed with monopolar cautery (The Huet Procedure) can also be used. Following surgery and histopathological assessment of the primary tumour and neck dissection surgical specimens, participants will be alloca…

Who can join: the full rules

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.

Where it's running

• Board of Trustees of the Leland Stanford Junior University
  Redwood City, California, United States
• Advent Health
  Orlando, Florida, United States
• MD Anderson Cancer Centre
  Houston, Texas, United States
• Metro South Health
  Brisbane, Australia
• Unicancer
  Paris, France
• Vivantes Klinikum
  Berlin, Germany

+7 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Mererid Evans, MBBch, PhD — Velindre NHS Trust

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.