Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS) (PATHOS)
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ClinicalTrials.gov Identifier: NCT02215265 |
Recruitment Status :
Recruiting
First Posted : August 13, 2014
Last Update Posted : July 21, 2023
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer | Drug: Cisplatin Radiation: Postoperative radiotherapy | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 1100 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase III Trial of Risk-stratified, Reduced Intensity Adjuvant Treatment in Patients Undergoing Transoral Surgery for Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer |
Actual Study Start Date : | October 2015 |
Estimated Primary Completion Date : | October 2026 |
Estimated Study Completion Date : | April 2027 |
Arm | Intervention/treatment |
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No Intervention: A: No adjuvant treatment
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.
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Active Comparator: B1: Postoperative radiotherapy 60 Gray
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. |
Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT) |
Experimental: B2: Postoperative radiotherapy 50 Gray
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. |
Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT) |
Active Comparator: C1: Postoperative radiotherapy 60 Gray with Cisplatin
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 |
Drug: Cisplatin
Chemotherapy Radiation: Postoperative radiotherapy Postoperative radiotherapy (PORT) |
Experimental: C2: Postoperative radiotherapy 60 Gray without chemotherapy
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 |
Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT) |
- MDADI/Overall survival co-primary endpoint [ Time Frame: At 12 months following treatment measured using the MD Anderson Dysphagia Inventory (MDADI) score. ]
- Swallowing panel including qualitative and quantitative swallowing assessments [ Time Frame: Baseline; 4 weeks (+/- 2 weeks) post-surgery, prior to start of any adjuvant treatment; 4 weeks (+/- 2 weeks) post treatment; 6 months (+/- 4 weeks) post treatment; 12 months (+/- 4 weeks) post treatment; 24 months (+/- 8 weeks) post treatment. ]Water swallow test
- QOL (using validated EORTC QLQ C30 and HN35 questionnaires) [ Time Frame: Baseline; 4 weeks (+/- 2 weeks) post-surgery, prior to start of any adjuvant treatment; 4 weeks (+/- 2 weeks) post treatment; 6 months (+/- 4 weeks) post treatment; 12 months (+/- 4 weeks) post treatment; 24 months (+/- 8 weeks) post treatment. ]Quality of Life (QOL) questions.
- Acute and late toxicity using CTACE version 4.03 [ Time Frame: Weekly during RT and at end of treatment; 4 weeks (+/- 2 weeks) post-surgery, prior to start of any adjuvant treatment; 4 weeks (+/- 2 weeks), 6 months (+/- 4 weeks), 12 months (+/- 4 weeks), and 24 months (+/- 8 weeks) post treatment. ]Toxicity assessment
- Disease Free Survival [ Time Frame: 6 months intervals ]Determined by clinical follow up as per standard guidelines
- Locoregional control [ Time Frame: 6 months intervals ]Determined by clinical follow up as per standard guidelines
- Distant Metastases [ Time Frame: 6 months intervals ]Determined by clinical follow up as per standard guidelines
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02215265
Principal Investigator: | Mererid Evans, MBBch, PhD | Velindre NHS Trust | |
Principal Investigator: | Terrence Jones, MBBS,MD | Aintree University Hospital |
Responsible Party: | Lisette Nixon, Trial Manager, Velindre NHS Trust |
ClinicalTrials.gov Identifier: | NCT02215265 |
Other Study ID Numbers: |
2014/VCC/0014 |
First Posted: | August 13, 2014 Key Record Dates |
Last Update Posted: | July 21, 2023 |
Last Verified: | July 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Human papillomavirus HPV positive oropharyngeal cancer |
Oropharyngeal Neoplasms Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms Head and Neck Neoplasms Neoplasms by Site Neoplasms |
Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases Cisplatin Antineoplastic Agents |