Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Oropharyngeal Cancer

Intervention / Treatment
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* Radiation: Radiation
* Procedure: Transoral Surgery (TOS) + Neck Dissection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 Arm study randomized in a 1:1 ratio
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1, Radiation +/- Chemotherapy<br>Standard Treatment (Radiation +/- Chemotherapy) | Radiation: Radiation<br>* Standard of Care: Radiation +/- Chemotherapy<br>* Other names: Chemotherapy, if required;|
| Experimental: Arm 2, TOS + Neck Dissection<br>Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required) | Procedure: Transoral Surgery (TOS) + Neck Dissection<br>* Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)<br>* Other names: Radiation, if required;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from randomization to death from any cause | 2 years | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transoral Surgery, Head and Neck Cancer