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

Primary Purpose

Oropharyngeal Cancer

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Radiation
Transoral Surgery (TOS) + Neck Dissection
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oropharyngeal Cancer focused on measuring Transoral Surgery, Head and Neck Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Gold Coast University Hospital
  • Royal Adelaide Hospital
  • Tom Baker Cancer Centre
  • BC Cancer
  • London Regional Cancer Program
  • Ottawa Hospital Research Institute
  • Sunnybrook Research Institute
  • University Health Network
  • Jewish General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1, Radiation +/- Chemotherapy

Arm 2, TOS + Neck Dissection

Arm Description

Standard Treatment (Radiation +/- Chemotherapy)

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

Outcomes

Primary Outcome Measures

Overall Survival
Time from randomization to death from any cause

Secondary Outcome Measures

Quality of Life 1 year post treatment
Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)
Progression free survival comparison with historical controls
Defined as time from randomization to death from any cause
Quality of life
Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
Quality of life
Quality of Life using the following questionnaire: EORTC QLQ C30
Quality of life
Quality of Life using the following questionnaire: H&N35 scale
Quality of life
Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
Quality of life
Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
Quality of life
Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
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
Feeding tube rate at 1 year
Measure other functional measurements such as feeding tube rate at 1 year
CTCAE Dysphagia grade
Measure other functional measurements such as CTCAE Dysphagia grade
Speech intelligibility
Measure other functional measurements such as speech intelligibility
Normalcy of diet
Measure other functional measurements such as normalcy of diet
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

Full Information

First Posted
June 28, 2017
Last Updated
October 4, 2023
Sponsor
Lawson Health Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03210103
Brief Title
Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer
Acronym
ORATOR2
Official Title
A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 26, 2018 (Actual)
Primary Completion Date
August 15, 2028 (Anticipated)
Study Completion Date
August 15, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lawson Health Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Cancer
Keywords
Transoral Surgery, Head and Neck Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
2 Arm study randomized in a 1:1 ratio
Masking
None (Open Label)
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1, Radiation +/- Chemotherapy
Arm Type
Active Comparator
Arm Description
Standard Treatment (Radiation +/- Chemotherapy)
Arm Title
Arm 2, TOS + Neck Dissection
Arm Type
Experimental
Arm Description
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Intervention Type
Radiation
Intervention Name(s)
Radiation
Other Intervention Name(s)
Chemotherapy, if required
Intervention Description
Standard of Care: Radiation +/- Chemotherapy
Intervention Type
Procedure
Intervention Name(s)
Transoral Surgery (TOS) + Neck Dissection
Other Intervention Name(s)
Radiation, if required
Intervention Description
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Primary Outcome Measure Information:
Title
Overall Survival
Description
Time from randomization to death from any cause
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Quality of Life 1 year post treatment
Description
Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)
Time Frame
1 year post treatment
Title
Progression free survival comparison with historical controls
Description
Defined as time from randomization to death from any cause
Time Frame
5 years
Title
Quality of life
Description
Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
Time Frame
Baseline to 5 years follow up
Title
Quality of life
Description
Quality of Life using the following questionnaire: EORTC QLQ C30
Time Frame
Baseline to 5 years follow up
Title
Quality of life
Description
Quality of Life using the following questionnaire: H&N35 scale
Time Frame
Baseline to 5 years follow up
Title
Quality of life
Description
Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
Time Frame
Baseline to 5 years follow up
Title
Quality of life
Description
Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
Time Frame
Baseline to 5 years follow up
Title
Quality of life
Description
Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
Time Frame
Baseline to 5 years follow up
Title
toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4
Description
To determine to 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
Title
Feeding tube rate at 1 year
Description
Measure other functional measurements such as feeding tube rate at 1 year
Time Frame
baseline to 1 year post treatment
Title
CTCAE Dysphagia grade
Description
Measure other functional measurements such as CTCAE Dysphagia grade
Time Frame
baseline to 5 years post treatment
Title
Speech intelligibility
Description
Measure other functional measurements such as speech intelligibility
Time Frame
baseline to 5 years post treatment
Title
Normalcy of diet
Description
Measure other functional measurements such as normalcy of diet
Time Frame
baseline to 5 years post treatment
Title
2 year progression-free survival comparison between Arm 1 and Arm 2
Description
Time from randomization to disease progress at any site or death from any cause
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Palma
Organizational Affiliation
Lawson Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gold Coast University Hospital
City
Gold Coast
State/Province
Queensland
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
BC Cancer
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1G1
Country
Canada
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Sunnybrook Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Jewish General Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35482348
Citation
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.
Results Reference
derived
PubMed Identifier
32059705
Citation
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.
Results Reference
derived

Learn more about this trial

Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer

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