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Oropharyngeal CancerORATOR2NCT03210103

Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer

A study testing Radiation and Transoral Surgery (TOS) + Neck Dissection in people with Oropharyngeal Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 9 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oropharyngeal Cancer
What is being tested?
Radiation and Transoral Surgery (TOS) + Neck Dissection
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
9 sitesin 2 countries
Study dates
26 Jan 2018to 15 Aug 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 12Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

Canada7 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1Y 4E9

  • Sunnybrook Research Institute

    Toronto, Ontario, M4N 3M5

  • University Health Network

    Toronto, Ontario, M5G 2C4

  • BC Cancer

    Vancouver, British Columbia, V5Z 1G1

Other trials in Canada

Australia2 sites

  • Royal Adelaide Hospital

    Adelaide

  • Gold Coast University Hospital

    Gold Coast, Queensland

Other trials in Australia

About this study

Official title: 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

Read the 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

Being tested
Radiation, Transoral Surgery (TOS) + Neck Dissection
Keywords
Transoral Surgery, Head and Neck Cancer
Medical subject headings
Oropharyngeal Neoplasms, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RadiationRadiation

    Also called Chemotherapy, if required

    Standard of Care: Radiation +/- Chemotherapy

  • Transoral Surgery (TOS) + Neck DissectionProcedure or surgery

    Also called Radiation, if required

    Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)

Study groups in NCT03210103
Study groupRoleWhat they receive
Arm 1, Radiation +/- ChemotherapyActive comparatorStandard Treatment (Radiation +/- Chemotherapy)
Receives: Radiation: Radiation
Arm 2, TOS + Neck DissectionExperimentalTransoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Receives: Procedure: Transoral Surgery (TOS) + Neck Dissection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Time from randomization to death from any cause

    Measured: 2 years

Secondary outcomes (14)

  1. Quality of Life 1 year post treatment

    Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)

    Measured: 1 year post treatment

  2. Progression free survival comparison with historical controls

    Defined as time from randomization to death from any cause

    Measured: 5 years

  3. Quality of life

    Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)

    Measured: Baseline to 5 years follow up

  4. Quality of life

    Quality of Life using the following questionnaire: EORTC QLQ C30

    Measured: Baseline to 5 years follow up

  5. Quality of life

    Quality of Life using the following questionnaire: H\&N35 scale

    Measured: Baseline to 5 years follow up

  6. Quality of life

    Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)

    Measured: Baseline to 5 years follow up

  7. Quality of life

    Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)

    Measured: Baseline to 5 years follow up

  8. Quality of life

    Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)

    Measured: Baseline to 5 years follow up

  9. 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

    Measured: Randomization until 5 years follow up

  10. Feeding tube rate at 1 year

    Measure other functional measurements such as feeding tube rate at 1 year

    Measured: baseline to 1 year post treatment

  11. CTCAE Dysphagia grade

    Measure other functional measurements such as CTCAE Dysphagia grade

    Measured: baseline to 5 years post treatment

  12. Speech intelligibility

    Measure other functional measurements such as speech intelligibility

    Measured: baseline to 5 years post treatment

  13. Normalcy of diet

    Measure other functional measurements such as normalcy of diet

    Measured: baseline to 5 years post treatment

  14. 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

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2017
  2. Study start26 Jan 2018
  3. Primary completion15 Aug 2028 (estimated)
  4. Study completion15 Aug 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
2 Arm study randomized in a 1:1 ratio
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03210103
Sponsor's protocol ID
ORATOR2
Acronym
ORATOR2
Status last verified
Dec 2025
First submitted
28 Jun 2017
Last updated
28 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Palma DA, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Eskander A, Higgins K, Karam I, Poon I, Husain Z, Enepekides D, Hier M, Richardson K, Mlynarek A, Johnson-Obaseki S, Gaudet M, Bayley A, Dowthwaite S, Jackson JE, Dzienis M, O'Neil J, Chandarana S, Banerjee R, Hart R, Chung J, Tenenholtz T, Le H, Yoo J, Mendez A, Winquist E, Kuruvilla S, Stewart P, Warner A, Mitchell S, Chen J, Parker C, Kwan K, Theurer J, Bahig H, Christopoulos A, Mendez LC, Sathya J, Hammond JA, Read N, Venkatesan V, Fung K, Nichols AC. Radiation vs. trans-oral surgery for treatment de-escalation in HPV-related oropharyngeal cancers: Primary analysis of the ORATOR2 randomized trial. Eur J Cancer. 2025 May 2;220:115343. doi: 10.1016/j.ejca.2025.115343. Epub 2025 Mar 10.

    PubMed 40121836

  • Palma DA, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Eskander A, Higgins K, Karam I, Poon I, Husain Z, Enepekides D, Hier M, Sultanem K, Richardson K, Mlynarek A, Johnson-Obaseki S, Odell M, Bayley A, Dowthwaite S, Jackson JE, Dzienis M, O'Neil J, Chandarana S, Banerjee R, Hart R, Chung J, Tenenholtz T, Krishnan S, Le H, Yoo J, Mendez A, Winquist E, Kuruvilla S, Stewart P, Warner A, Mitchell S, Chen J, Parker C, Wehrli B, Kwan K, Theurer J, Sathya J, Hammond JA, Read N, Venkatesan V, MacNeil SD, Fung K, Nichols AC. Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2022 Jun 1;8(6):1-7. doi: 10.1001/jamaoncol.2022.0615.

    PubMed 35482348

  • Nichols AC, Lang P, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Fung K, de Almeida JR, Bayley A, Goldstein DP, Eskander A, Husain Z, Bahig H, Christopoulous A, Hier M, Sultanem K, Richardson K, Mlynarek A, Krishnan S, Le H, Yoo J, MacNeil SD, Mendez A, Winquist E, Read N, Venkatesan V, Kuruvilla S, Warner A, Mitchell S, Corsten M, Rajaraman M, Johnson-Obaseki S, Eapen L, Odell M, Chandarana S, Banerjee R, Dort J, Matthews TW, Hart R, Kerr P, Dowthwaite S, Gupta M, Zhang H, Wright J, Parker C, Wehrli B, Kwan K, Theurer J, Palma DA. Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial. BMC Cancer. 2020 Feb 14;20(1):125. doi: 10.1186/s12885-020-6607-z.

    PubMed 32059705

Questions about this trial

What is this clinical trial studying?

A study testing Radiation and Transoral Surgery (TOS) + Neck Dissection in people with Oropharyngeal Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03210103, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.

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