Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer (ORATOR2)

January 26, 2026 updated by: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia
        • Royal Adelaide Hospital
    • Queensland
      • Gold Coast, Queensland, Australia
        • Gold Coast University Hospital
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1G1
        • BC Cancer
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Ottawa, Ontario, Canada, K1Y 4E9
        • Ottawa Hospital Research Institute
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute
      • Toronto, Ontario, Canada, M5G 2C4
        • University Health Network
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1, Radiation +/- Chemotherapy
Standard Treatment (Radiation +/- Chemotherapy)
Radiation: Radiation
Standard of Care: Radiation +/- Chemotherapy
Other Names:
  • Chemotherapy, if required
Experimental: Arm 2, TOS + Neck Dissection
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Procedure: Transoral Surgery (TOS) + Neck Dissection
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Other Names:
  • Radiation, if required

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 2 years
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
Time Frame: 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
Time Frame: 5 years
Defined as time from randomization to death from any cause
5 years
Quality of life
Time Frame: Baseline to 5 years follow up
Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
Baseline to 5 years follow up
Quality of life
Time Frame: Baseline to 5 years follow up
Quality of Life using the following questionnaire: EORTC QLQ C30
Baseline to 5 years follow up
Quality of life
Time Frame: Baseline to 5 years follow up
Quality of Life using the following questionnaire: H&N35 scale
Baseline to 5 years follow up
Quality of life
Time Frame: Baseline to 5 years follow up
Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
Baseline to 5 years follow up
Quality of life
Time Frame: Baseline to 5 years follow up
Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
Baseline to 5 years follow up
Quality of life
Time Frame: Baseline to 5 years follow up
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
Time Frame: 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
Randomization until 5 years follow up
Feeding tube rate at 1 year
Time Frame: baseline to 1 year post treatment
Measure other functional measurements such as feeding tube rate at 1 year
baseline to 1 year post treatment
CTCAE Dysphagia grade
Time Frame: baseline to 5 years post treatment
Measure other functional measurements such as CTCAE Dysphagia grade
baseline to 5 years post treatment
Speech intelligibility
Time Frame: baseline to 5 years post treatment
Measure other functional measurements such as speech intelligibility
baseline to 5 years post treatment
Normalcy of diet
Time Frame: baseline to 5 years post treatment
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 Frame: 2 years
Time from randomization to disease progress at any site or death from any cause
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Investigators

  • Principal Investigator: David Palma, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 26, 2018

Primary Completion (Estimated)

August 15, 2028

Study Completion (Estimated)

August 15, 2028

Study Registration Dates

First Submitted

June 28, 2017

First Submitted That Met QC Criteria

July 4, 2017

First Posted (Actual)

July 6, 2017

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 26, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORATOR2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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