Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer

NCT ID: NCT03210103

Last Updated: 2026-01-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-26

Study Completion Date

2028-08-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Oropharyngeal Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

2 Arm study randomized in a 1:1 ratio
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm 1, Radiation +/- Chemotherapy

Standard Treatment (Radiation +/- Chemotherapy)

Group Type ACTIVE_COMPARATOR

Radiation

Intervention Type RADIATION

Standard of Care: Radiation +/- Chemotherapy

Arm 2, TOS + Neck Dissection

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

Group Type EXPERIMENTAL

Transoral Surgery (TOS) + Neck Dissection

Intervention Type PROCEDURE

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Radiation

Standard of Care: Radiation +/- Chemotherapy

Intervention Type RADIATION

Transoral Surgery (TOS) + Neck Dissection

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

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Chemotherapy, if required Radiation, if required

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

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

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

David Palma

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, , Australia

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

BC Cancer

Vancouver, British Columbia, Canada

Site Status

London Regional Cancer Program

London, Ontario, Canada

Site Status

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Site Status

Sunnybrook Research Institute

Toronto, Ontario, Canada

Site Status

University Health Network

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia Canada

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40121836 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35482348 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32059705 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ORATOR2

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.