Clinical Trials /

Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer

NCT03210103

Description:

The goal of this randomized treatment de-escalation study is to formally compare outcomes in HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary surgical approach, to provide a high level of evidence to guide the selection of treatment options for a subsequent phase III trial

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer
  • Official Title: A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)

Clinical Trial IDs

  • ORG STUDY ID: ORATOR2
  • NCT ID: NCT03210103

Conditions

  • Oropharyngeal Cancer

Purpose

The goal of this randomized treatment de-escalation study is to formally compare outcomes in HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary surgical approach, to provide a high level of evidence to guide the selection of treatment options for a subsequent phase III trial

Detailed Description

      The goal of this randomized treatment de-escalation study is to formally compare outcomes in
      HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary
      surgical approach, to provide a high level of evidence to guide the selection of treatment
      options for a subsequent phase III trial

      The study will compare Progression free survival relative to historical controls for
      de-intensified primary radiotherapy [60 GY +/- chemotherapy] versus transoral surgery (TOS)
      and neck dissection [+/- adjuvant 50Gy radiotherapy] in patients with early T-stage
      HPV-positive squamous cell carcinoma of the oropharynx and to compare quality of life (QOL)
      profiles.

      The study will require a sample size of 120 patients randomized in a 1:1 ratio between the
      two arms. Arm 1 (radiotherapy +/1 chemotherapy) and Arm 2 (TOS)

      Patients will be followed for a total of 5 years
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1, Radiation +/- ChemotherapyActive ComparatorStandard Treatment (Radiation +/- Chemotherapy)
    Arm 2, TOS + Neck DissectionExperimentalTransoral Surgery (TOS) + Neck Dissection (plus radiation, if required)

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Age 18 years or older
      
                -  willing to provide informed consent
      
                -  ECOG performance status 0-2
      
                -  Histologically confirmed squamous cell carcinoma
      
                -  P16 positive, or HPV positive
      
                -  Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue,
                   walls of oropharynx)
      
                -  Eligible for curative intent treatment, with likely negative resection margins at
                   surgery. For patients where adequate transoral access is in question, they will first
                   undergo an examination under anesthesia prior to randomization to ensure adequate
                   exposure can be obtained.
      
                -  Smokers and non-smokers are included. Patients will be stratified by ,<10 pack years
                   smoking history versus > or equal to 10 pack years.
      
                -  Tumor stage (AJCC 8th edition): T1 or T2
      
                -  Nodal stage (AJCC 8th edition): N0, N1, or N2
      
                -  For patients who may require chemotherapy (ie, patients with multiple lymph nodes
                   positive or a single node more than 3 cm in size, in any plane, CBC/differential
                   within 4 weeks prior to randomization with adequate bone marrow function, hepatic, and
                   renal function defined as: Hemoglobin ≥ 80 g/L; Absolute neutrophil count ≥ 1.5 x 10
                   9/L, platelets ≥ 100 x 10 9/L, bilirubin ≤ 35 umol/L, AST or ALT ≤ 3 x the upper limit
                   of normal; serum creatinine ≤ 130 umol/L or creatinine clearance ≥ 50 ml/min
      
                -  patients assessed at head and neck multidisciplinary clinic (with assessment by
                   radiation oncologist and surgeon) and presented at multidisciplinary tumor board prior
                   to randomization
      
              Exclusion Criteria:
      
                -  unambiguous clinical or radiological evidence of extranodaal extension on
                   pre-treatment imaging. This includes the presence of matted notes, defined as 3 or
                   more nodes that are abutting with loss of intervening fat planes
      
                -  Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy
                   or surgery
      
                -  prior history of head and neck cancer within 5 years
      
                -  prior head and neck radiation at any time
      
                -  metastatic disease
      
                -  inability to attend full course of radiotherapy or follow up visits
      
                -  prior invasive malignant disease unless disease-free for at least 5 years or more,
                   with the exception of non-melanoma skin cancer
      
                -  pregnant or lactating women
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:2 year progression free survival (comparison with historical controls)
      Time Frame:2 years
      Safety Issue:
      Description:Time from randomization to disease progress at any site or death from any cause

      Secondary Outcome Measures

      Measure:Quality of Life 1 year post treatment
      Time Frame:1 year post treatment
      Safety Issue:
      Description:Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)
      Measure:Overall Survival
      Time Frame:5 years
      Safety Issue:
      Description:Defined as time from randomization to death from any cause
      Measure:Quality of life
      Time Frame:Baseline to 5 years follow up
      Safety Issue:
      Description:Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
      Measure:Quality of life
      Time Frame:Baseline to 5 years follow up
      Safety Issue:
      Description:Quality of Life using the following questionnaire: EORTC QLQ C30
      Measure:Quality of life
      Time Frame:Baseline to 5 years follow up
      Safety Issue:
      Description:Quality of Life using the following questionnaire: H&N35 scale
      Measure:Quality of life
      Time Frame:Baseline to 5 years follow up
      Safety Issue:
      Description:Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
      Measure:Quality of life
      Time Frame:Baseline to 5 years follow up
      Safety Issue:
      Description:Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
      Measure:Quality of life
      Time Frame:Baseline to 5 years follow up
      Safety Issue:
      Description:Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
      Measure:toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4
      Time Frame:Randomization until 5 years follow up
      Safety Issue:
      Description:To determine to toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4
      Measure:Feeding tube rate at 1 year
      Time Frame:baseline to 1 year post treatment
      Safety Issue:
      Description:Measure other functional measurements such as feeding tube rate at 1 year
      Measure:CTCAE Dysphagia grade
      Time Frame:baseline to 5 years post treatment
      Safety Issue:
      Description:Measure other functional measurements such as CTCAE Dysphagia grade
      Measure:Speech intelligibility
      Time Frame:baseline to 5 years post treatment
      Safety Issue:
      Description:Measure other functional measurements such as speech intelligibility
      Measure:Normalcy of diet
      Time Frame:baseline to 5 years post treatment
      Safety Issue:
      Description:Measure other functional measurements such as normalcy of diet
      Measure:2 year progression-free survival comparison between Arm 1 and Arm 2
      Time Frame:2 years
      Safety Issue:
      Description:Time from randomization to disease progress at any site or death from any cause

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Lawson Health Research Institute

      Trial Keywords

      • Transoral Surgery
      • Head and Neck Cancer

      Last Updated

      <p/>