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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02215265




Registration number
NCT02215265
Ethics application status
Date submitted
11/08/2014
Date registered
13/08/2014
Date last updated
24/09/2020

Titles & IDs
Public title
Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS)
Scientific title
A Phase III Trial of Risk-stratified, Reduced Intensity Adjuvant Treatment in Patients Undergoing Transoral Surgery for Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer
Secondary ID [1] 0 0
2014/VCC/0014
Universal Trial Number (UTN)
Trial acronym
PATHOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Other - Postoperative radiotherapy

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.

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.

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.

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

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


Treatment: Drugs: Cisplatin
Chemotherapy

Treatment: Other: Postoperative radiotherapy
Postoperative radiotherapy (PORT)

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MDADI/Overall survival co-primary endpoint
Timepoint [1] 0 0
At 12 months following treatment measured using the MD Anderson Dysphagia Inventory (MDADI) score.
Secondary outcome [1] 0 0
Swallowing panel including qualitative and quantitative swallowing assessments - Water swallow test
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
QOL (using validated EORTC QLQ C30 and HN35 questionnaires) - Quality of Life (QOL) questions.
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Acute and late toxicity using CTACE version 4.03 - Toxicity assessment
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Disease Free Survival - Determined by clinical follow up as per standard guidelines
Timepoint [4] 0 0
6 months intervals
Secondary outcome [5] 0 0
Locoregional control - Determined by clinical follow up as per standard guidelines
Timepoint [5] 0 0
6 months intervals
Secondary outcome [6] 0 0
Distant Metastases - Determined by clinical follow up as per standard guidelines
Timepoint [6] 0 0
6 months intervals

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Metro South Health - Brisbane
Recruitment postcode(s) [1] 0 0
QLD 4113 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussels
Country [4] 0 0
France
State/province [4] 0 0
Paris
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Dorset
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Bath
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Birmingham
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Blackburn
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Bristol
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Cambridge
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Cardiff
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Cottingham
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Derby
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Edinburgh
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Guildford
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Leeds
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Liverpool
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Llantrisant
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Manchester
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Middlesbrough
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Newcastle upon Tyne
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Newport
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Oxford
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Plymouth
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Portsmouth
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Reading
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Southampton
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Sunderland
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Other
Name
Lisette Nixon
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
UNICANCER
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
AdventHealth
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Leipzig
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Princess Alexandra Hospital, Brisbane, Australia
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
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 the non-inferiority of reducing the intensity of adjuvant treatment protocols
in terms of overall survival in the reduced intensity treatment arms.
Trial website
https://clinicaltrials.gov/show/NCT02215265
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mererid Evans, MBBch, PhD
Address 0 0
Velindre NHS Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02215265