Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer
- Conditions
- Oropharyngeal Cancer
- Interventions
- Procedure: Transoral Surgery (TOS) + Neck DissectionRadiation: Radiation
- Registration Number
- NCT03210103
- Lead Sponsor
- Lawson Health Research Institute
- Brief Summary
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 overall survival rates 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 140 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 61
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2, TOS + Neck Dissection Transoral Surgery (TOS) + Neck Dissection Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required) Arm 1, Radiation +/- Chemotherapy Radiation Standard Treatment (Radiation +/- Chemotherapy)
- Primary Outcome Measures
Name Time Method Overall Survival 2 years Time from randomization to death from any cause
- Secondary Outcome Measures
Name Time Method CTCAE Dysphagia grade baseline to 5 years post treatment Measure other functional measurements such as CTCAE Dysphagia grade
Quality of life Baseline to 5 years follow up Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
Speech intelligibility baseline to 5 years post treatment Measure other functional measurements such as speech intelligibility
Progression free survival comparison with historical controls 5 years Defined as time from randomization to death from any cause
Quality of Life 1 year post treatment 1 year post treatment Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)
Feeding tube rate at 1 year baseline to 1 year post treatment Measure other functional measurements such as feeding tube rate at 1 year
toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4 Randomization until 5 years follow up To determine to toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4
Normalcy of diet baseline to 5 years post treatment Measure other functional measurements such as normalcy of diet
2 year progression-free survival comparison between Arm 1 and Arm 2 2 years Time from randomization to disease progress at any site or death from any cause
Trial Locations
- Locations (9)
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Gold Coast University Hospital
🇦🇺Gold Coast, Queensland, Australia
BC Cancer
🇨🇦Vancouver, British Columbia, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
University Health Network
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada