NCT03210103

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

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
61

participants targeted

Target at P25-P50 for not_applicable

Timeline
27mo left

Started Jan 2018

Longer than P75 for not_applicable

Geographic Reach
2 countries

9 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress78%
Jan 2018Aug 2028

First Submitted

Initial submission to the registry

June 28, 2017

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 6, 2017

Completed
7 months until next milestone

Study Start

First participant enrolled

January 26, 2018

Completed
10.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2028

Last Updated

January 28, 2026

Status Verified

December 1, 2025

Enrollment Period

10.6 years

First QC Date

June 28, 2017

Last Update Submit

January 26, 2026

Conditions

Oropharyngeal Cancer

Keywords

Transoral SurgeryHead and Neck Cancer

Outcome Measures

Primary Outcomes (1)

  • Overall Survival

    Time from randomization to death from any cause

    2 years

Secondary Outcomes (14)

  • Quality of Life 1 year post treatment

    1 year post treatment

  • Progression free survival comparison with historical controls

    5 years

  • Quality of life

    Baseline to 5 years follow up

  • Quality of life

    Baseline to 5 years follow up

  • Quality of life

    Baseline to 5 years follow up

  • +9 more secondary outcomes

Study Arms (2)

Arm 1, Radiation +/- Chemotherapy

ACTIVE COMPARATOR

Standard Treatment (Radiation +/- Chemotherapy)

Radiation: Radiation

Arm 2, TOS + Neck Dissection

EXPERIMENTAL

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

Procedure: Transoral Surgery (TOS) + Neck Dissection

Interventions

RadiationRADIATION

Standard of Care: Radiation +/- Chemotherapy

Also known as: Chemotherapy, if required
Arm 1, Radiation +/- Chemotherapy
Transoral Surgery (TOS) + Neck DissectionPROCEDURE

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

Also known as: Radiation, if required
Arm 2, TOS + Neck Dissection

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BC Cancer

Vancouver, British Columbia, V5Z 1G1, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (3)

  • 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.

    PMID: 40121836DERIVED

  • 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.

    PMID: 35482348DERIVED

  • 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.

    PMID: 32059705DERIVED

MeSH Terms

Conditions

Oropharyngeal NeoplasmsHead and Neck Neoplasms

Interventions

RadiationDrug TherapyNeck Dissection

Condition Hierarchy (Ancestors)

Pharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsNeoplasms by SiteNeoplasmsPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Physical PhenomenaTherapeuticsLymph Node ExcisionSurgical Procedures, OperativeOtorhinolaryngologic Surgical Procedures

Study Officials

  • David Palma

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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 2 Arm study randomized in a 1:1 ratio
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 28, 2017

First Posted

July 6, 2017

Study Start

January 26, 2018

Primary Completion (Estimated)

August 15, 2028

Study Completion (Estimated)

August 15, 2028

Last Updated

January 28, 2026

Record last verified: 2025-12

Locations

CA(7)AU(2)