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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 : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Lisette Nixon, Velindre NHS Trust

Brief 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 feasibility of recruitment- if the phase II recruits successfully, PATHOS will continue to a Phase III study aiming to show non-inferiority of 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 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II/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 : February 2020
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
No Intervention: No adjuvant treatment
Group A
Active Comparator: 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), N2a (metastasis in single ipsilateral node 31-60 mm diameter) or N2b (metastasis in multiple ipsilateral nodes <61 mm diameter) disease, tumours with evidence of perineural and/or vascular invasion, or close margins (1-5mm) around the primary tumour specimen but with negative marginal biopsies.

Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT)

Experimental: 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), N2a (metastasis in single ipsilateral node 31-60 mm diameter) or N2b (metastasis in multiple ipsilateral nodes <61 mm diameter) disease, tumours with evidence of perineural and/or vascular invasion, or close margins (1-5mm) around the primary tumour specimen but with negative marginal biopsies.

Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT)

Active Comparator: 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: positive (<1mm) margins around the primary tumour specimen but with negative marginal biopsies and/or evidence of cervical lymph node extracapsular spread.

Drug: Cisplatin
Chemotherapy

Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT)

Experimental: 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: positive (<1mm) margins around the primary tumour specimen but with negative marginal biopsies and/or evidence of cervical lymph node extracapsular spread.

Radiation: Postoperative radiotherapy
Postoperative radiotherapy (PORT)




Primary Outcome Measures :
  1. Phase II: Patient-reported swallowing outcome [ Time Frame: At 12 months following treatment measured using the MD Anderson Dysphagia Inventory (MDADI) score. ]

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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. ]
  4. Overall survival [ Time Frame: 6 months intervals ]
  5. Disease Free Survival [ Time Frame: 6 months intervals ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of squamous cell carcinoma of the oropharynx
  • HPV positive on central testing (section 6.4)
  • UICC TNM (7th edition) stage T1-T3, N0-N2b tumours of the oropharynx Staging should be based on cross sectional imaging investigations carried out within 6 weeks of study entry*
  • Local MDT decision to treat with primary transoral resection and neck dissection
  • Patients considered fit for surgery and adjuvant treatment by the local MDT
  • Aged 18 or over
  • Written informed consent provided * Please Note: Current smokers with N2b disease (including smokers up to 2 years before diagnosis) are not eligible to be included

Exclusion Criteria:

  • HPV negative squamous cell carcinomas of the head and neck
  • Patients with T4 primary oropharyngeal tumours and/or T1-T3 tumours where transoral surgery is considered not feasible
  • N2c-N3 nodal disease
  • Unresectable retropharyngeal node involvement
  • Current smokers with N2b disease (including smokers up to 2 years before diagnosis)
  • Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction
  • Patients with distant metastatic disease (UICC TNM stage IVC 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

Information from the National Library of Medicine

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


Locations
United Kingdom
Poole Hospital NHS Foundation Trust Recruiting
Poole, Dorset, United Kingdom, BH15 2JB
Contact: Emma King, Dr       emmabarker@doctors.org.uk   
Royal United Hospitals Bath NHS Foundation Trust Recruiting
Bath, United Kingdom, BA1 3NH
Contact: Emma De Winton, Dr       emma.dewinton@nhs.net   
Queen Elizabeth Hospital Not yet recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Andrew Hartley, Dr         
University Hospitals Bristol NHS Foundation Trust Recruiting
Bristol, United Kingdom, BS2 8ED
Contact: Matthew Beasley, Dr       Matthew.Beasley@UHBristol.nhs.uk   
Cambridge University Hospitals NHS Foundation Trust Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Irune Ekpemi, Dr       ekpemi.irune@addenbrookes.nhs.uk   
Velindre Cancer Centre Not yet recruiting
Cardiff, United Kingdom, CF14 2TL
Contact: Waheeda Owadally, Dr       Waheeda.Owadally@wales.nhs.uk   
HPV Research Group Section of Pathology Cardiff University ,School of Medicine Not yet recruiting
Cardiff, United Kingdom, CF14 4XN
Contact: Ned Powell, Dr       PowellNG@cardiff.ac.uk   
Cardiff and Vale University Local Health Board Recruiting
Cardiff, United Kingdom, CF14 4XW
Contact: David Owens, Dr       david.owens2@wales.nhs.uk   
Wales Cancer Trials Unit Not yet recruiting
Cardiff, United Kingdom, CF14 4YS
Contact: Chris Hurt    02920687471    HurtCN@cf.ac.uk   
Velindre NHS Trust Not yet recruiting
Cardiff, United Kingdom, CF142TL
Contact: Nachi Palaniappan, Dr       Nachi.Palaniappan@wales.nhs.uk   
Castle Hill Hospital Recruiting
Cottingham, United Kingdom, HU16 5JQ
Contact: Lorcan O'Toole, Dr       lorcan.otoole@hey.nhs.uk   
Derby Teaching Hospitals NHS Foundation Trust Recruiting
Derby, United Kingdom, DE22 3DT
Contact: Sean Mortimore, Dr       sean.mortimore@nhs.net   
Aintree University Hospitals NHS Foundation Trust Recruiting
Liverpool, United Kingdom, L3 9TA
Contact: Terry Jones, Professor       T.M.Jones@liverpool.ac.uk   
Cwm Taf University Health Board Recruiting
Llantrisant, United Kingdom, CF72 8XR
Contact: Sandeep Berry, Dr       sandeep.berry2@wales.nhs.uk   
Barts Health NHS Trust Not yet recruiting
London, United Kingdom, E1 1RD
Contact: Paul Stimpson, Dr       paul.stimpson2@bartshealth.nhs.uk   
Central Manchester University Hospital NHS Foundation Trust Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Jarrod Homer, Professor       jarrod.j.homer@manchester.ac.uk   
The Christie NHS Foundation Trust Not yet recruiting
Manchester, United Kingdom, M20 4BX
Contact: David Thomson, Dr       david.thomson@christie.nhs.uk   
The James Cook University Hospital Recruiting
Middlesbrough, United Kingdom, TS4 3BW
Contact: Shane Lester, Mr       shanelester@nhs.net   
Newcastle upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle upon Tyne, United Kingdom, NE7 7DN
Contact: Rebecca Goranova, Dr       Rebecca.goronova@nuth.nhs.uk   
Institute of Health and Society Not yet recruiting
Newcastle, United Kingdom, NE2 4AX
Contact: Jo Patterson, Dr       joanne.patterson@newcastle.ac.uk   
Centre for Oral Health Research Newcastle University Not yet recruiting
Newcastle, United Kingdom, NE24BW
Contact: Conrad Robinson, Dr       max.robinson@newcastle.ac.uk   
Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, United Kingdom, OX3 7LD
Contact: Stuart Winter, Dr       stuart.winter@ouh.nhs.uk   
Queen Alexandra Hospital Recruiting
Portsmouth, United Kingdom, PO6 3LY
Contact: Costa Repanos, Mr       costa.repanos@porthosp.nhs.uk   
Royal Berkshire Hospital Not yet recruiting
Reading, United Kingdom, RG1 5AN
Contact: Alice Freebairn, Dr       alice.freebairn@royalberkshire.nhs.uk   
Sunderland Royal Hospital Recruiting
Sunderland, United Kingdom, SR4 7TP
Contact: Helen Cocks, Dr       helen.cocks@chsft.nhs.uk   
Abertawe Bro Morgannwg University Health Board Recruiting
Swansea, United Kingdom, SA2 8QA
Contact: Conor Marnane, Dr       conor.marnane@wales.nhs.uk   
Sponsors and Collaborators
Lisette Nixon
Investigators
Principal Investigator: Mererid Evans, PhD Velindre NHS Trust

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lisette Nixon, Trial Manager, Velindre NHS Trust
ClinicalTrials.gov Identifier: NCT02215265     History of Changes
Other Study ID Numbers: 2014/VCC/0014
First Posted: August 13, 2014    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lisette Nixon, Velindre NHS Trust:
Human papillomavirus HPV positive oropharyngeal cancer

Additional relevant MeSH terms:
Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Antineoplastic Agents