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

• Status: Recruiting
• Trial end date: 2027-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The main objectives of the PATHOS study are:

To assess whether swallowing function can be improved following transoral resection of HPV-positive OPSCC, by reducing the intensity of adjuvant treatment protocols. The aim is to personalise treatment, based on disease biology (HPV status and pathology findings), to optimise patient outcomes.

To demonstrate the non-inferiority of reducing the intensity of adjuvant treatment protocols in terms of overall survival in the reduced intensity treatment arms.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lisette Nixon
• Collaborators: AdventHealth; European Organisation for Research and Treatment of Cancer - EORTC; Princess Alexandra Hospital, Brisbane, Australia; UNICANCER; University of Leipzig
• Treatments: Cisplatin

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. [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.

• 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 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.