ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02215265
Recruitment Status : Not yet recruiting
First Posted : August 13, 2014
Last Update Posted : August 13, 2014
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
Study Start Date : December 2014
Estimated Primary Completion Date : December 2019

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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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
University Hospitals Bristol NHS Foundation Trust Not yet recruiting
Bristol, United Kingdom, BS2 8ED
Contact: Matthew Beasley, Dr       Matthew.Beasley@UHBristol.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   
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   
Aintree University Hospitals NHS Foundation Trust Not yet recruiting
Liverpool, United Kingdom, L3 9TA
Contact: Terry Jones, Professor       T.M.Jones@liverpool.ac.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   
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: August 13, 2014
Last Verified: August 2014

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