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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 : Recruiting
First Posted : August 13, 2014
Last Update Posted : September 24, 2020
Sponsor:
Collaborators:
UNICANCER
European Organisation for Research and Treatment of Cancer - EORTC
AdventHealth
University of Leipzig
Princess Alexandra Hospital, Brisbane, Australia
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 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

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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

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
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.

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)




Primary Outcome Measures :
  1. MDADI/Overall survival co-primary endpoint [ 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. ]
    Toxicity assessment

  4. Disease Free Survival [ Time Frame: 6 months intervals ]
    Determined by clinical follow up as per standard guidelines

  5. Locoregional control [ Time Frame: 6 months intervals ]
    Determined by clinical follow up as per standard guidelines

  6. Distant Metastases [ Time Frame: 6 months intervals ]
    Determined by clinical follow up as per standard guidelines



Information from the National Library of Medicine

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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 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.

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
Show Show 41 study locations
Sponsors and Collaborators
Lisette Nixon
UNICANCER
European Organisation for Research and Treatment of Cancer - EORTC
AdventHealth
University of Leipzig
Princess Alexandra Hospital, Brisbane, Australia
Investigators
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Principal Investigator: Mererid Evans, MBBch, PhD Velindre NHS Trust
Principal Investigator: Terrence Jones, MBBS,MD Aintree University Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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: September 24, 2020
Last Verified: September 2020

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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:
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Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Antineoplastic Agents