Head and Neck CancerPhase 2NCT04220749
Radiotherapy vs. Trans-Oral Surgery for HPV-Negative Oropharyngeal Squamous Cell Carcinoma
A Phase 2 study testing Radiation and Trans-Oral Surgery (TOS) + Neck Dissection in people with Head and Neck Cancer and Oropharyngeal Squamous Cell Carcinoma, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
The goal of this randomized phase II study is a formal comparison of radiotherapy versus trans-oral surgery as the primary treatment of HPV-negative patients with early-stage oropharyngeal carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Oropharyngeal Squamous Cell Carcinoma
- What is being tested?
- Radiation and Trans-Oral Surgery (TOS) + Neck Dissection
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteCanada
- Study dates
- 25 Jun 2020to Feb 2028
- Phase
- Phase 2
- 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
- HPV-negative tumor, as determined by: negative p16 status, real time PCR or in-situ hybridization. Central confirmation is not required prior to randomization. Equivocal/uncertain HPV status will be allowed on trial.
- Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx)
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- Tumor stage: T1 or T2, with likely negative resection margins at surgery
- Nodal stage: N0-3. Patients with positive nodal disease and extranodal extension on imaging may be included at the surgeon's discretion, if the nodal disease is deemed resectable by the operating surgeon.
- 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.
- Blood work obtained within 4 weeks prior to randomization, with adequate bone marrow function, hepatic, and renal function, as determined by the investigator.
- Patient assessed by a radiation oncologist and surgeon and presented at multidisciplinary tumor board prior to randomization. If not feasible, case can be discussed with study Principal Investigator.
Who cannot join
- 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
- Unable or unwilling to complete QOL questionnaires
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
London Regional Cancer Program
London, Ontario, N6A 5W9
Danielle MacNeil, MD, 519-658-8600, Danielle.Macneil@lhsc.on.ca
About this study
Official title: A Phase II Randomized Trial for HPV-Negative Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR)
The goal of this randomized phase II study is a formal comparison of radiotherapy versus trans-oral surgery as the primary treatment of HPV-negative patients with early-stage oropharyngeal carcinoma.
Read the detailed description
This study is designed as a randomized phase II study. Patients will be randomized between current standard of care treatment (Arm 1) vs. TOS (Arm 2) in a 1:1 ratio. Additionally, patients will be stratified according to T stage (T1 vs. T2); N stage (N0/1 vs. N2/3)
The randomized phase II design is required for three reasons:
- The randomization will provide an appropriate control group to serve as a comparator for the experimental arm. Historical or contemporaneous non-randomized controls would not be appropriate due to the multitude of biases that could be introduced by patient selection and other confounders.
- A small sample size will allow for adequate power to assess for progression-free survival, and also an assessment of quality of life, overall survival and toxicity.
- The results will allow for a decision as to whether a multi-institutional phase III trial is warranted, and inform the design of such a trial.
- Being tested
- Radiation, Trans-Oral Surgery (TOS) + Neck Dissection
- Keywords
- Radiotherapy, Trans-Oral Surgery, HPV-Negative, Randomized
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
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
Trans-Oral Surgery (TOS) + Neck DissectionProcedure or surgery
Also called Radiation, if required
Trans-Oral Surgery (TOS) + Neck Dissection (plus radiation, if required)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1, Radiation +/- Chemotherapy | Active comparator | Standard Treatment (Radiation +/- Chemotherapy) Receives: Radiation: Radiation |
| Arm 2, TOS + Neck Dissection | Experimental | Trans-oral Surgery (TOS) + Neck Dissection (plus radiation is required) Receives: Procedure: Trans-Oral Surgery (TOS) + Neck Dissection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Specific Survival
Time from randomization to death from cancer
Measured: 5 years
Secondary outcomes (14)
Overall Survival
Time from randomization to death from any cause
Measured: 5 years
Progression-Free Survival
Defined as time from randomization to death from any cause
Measured: 5 years
Local-Regional Failure
Defined as time from randomization to first local-regional failure (analyzed as cumulative incidence function with death as competing event)
Measured: 5 years
Distant Failure
Defined as time from randomization to first distant failure or metastasis (analyzed as cumulative incidence function with death as competing event)
Measured: 5 years
Any Failure
Defined as time from randomization to first local-regional failure or distant failure, whichever occurs first (analyzed as cumulative incidence function with death as competing event)
Measured: 5 years
Quality of Life
Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
Measured: Baseline to 5 years follow up
Quality of Life
Quality of Life using the following questionnaire: EORTC QLQ-C30
Measured: Baseline to 5 years follow up
Quality of Life
Quality of Life using the following questionnaire: H\&N35 scale
Measured: Baseline to 5 years follow up
Quality of Life
Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
Measured: Baseline to 5 years follow up
Quality of Life
Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
Measured: Baseline to 5 years follow up
Quality of Life
Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
Measured: Baseline to 5 years follow up
Toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4
To determine 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
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
CTCAE Dysphagia Grade
Measure other functional measurements such as CTCAE Dysphagia grade
Measured: Baseline to 5 years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start25 Jun 2020
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- 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
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Danielle MacNeil, M.D., Principal investigator, London Regional Cancer Program, London Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04220749
- Sponsor's protocol ID
- ORATOR 3
- Status last verified
- Sep 2020
- First submitted
- 6 Jan 2020
- Last updated
- 4 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Trial for HPV-Negative Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR)
- ClinicalTrials.gov ID
- NCT04220749
- Acronym / sponsor ID
- ORATOR 3
- Keywords
- Radiotherapy, Trans-Oral Surgery, HPV-Negative, Randomized
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 25 Jun 2020 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 7 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized phase II study is a formal comparison of radiotherapy versus trans-oral surgery as the primary treatment of HPV-negative patients with early-stage oropharyngeal carcinoma.
Detailed description
This study is designed as a randomized phase II study. Patients will be randomized between current standard of care treatment (Arm 1) vs. TOS (Arm 2) in a 1:1 ratio. Additionally, patients will be stratified according to T stage (T1 vs. T2); N stage (N0/1 vs. N2/3)
The randomized phase II design is required for three reasons:
- The randomization will provide an appropriate control group to serve as a comparator for the experimental arm. Historical or contemporaneous non-randomized controls would not be appropriate due to the multitude of biases that could be introduced by patient selection and other confounders.
- A small sample size will allow for adequate power to assess for progression-free survival, and also an assessment of quality of life, overall survival and toxicity.
- The results will allow for a decision as to whether a multi-institutional phase III trial is warranted, and inform the design of such a trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 2 Arm study randomized in a 1:1 ratio
| Arm | Type | Receives |
|---|---|---|
| Arm 1, Radiation +/- Chemotherapy | Active comparator | Radiation: RadiationStandard Treatment (Radiation +/- Chemotherapy) |
| Arm 2, TOS + Neck Dissection | Experimental | Procedure: Trans-Oral Surgery (TOS) + Neck DissectionTrans-oral Surgery (TOS) + Neck Dissection (plus radiation is required) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 years or older
- Willing to provide informed consent
- ECOG performance status 0-2
- Histologically confirmed squamous cell carcinoma
- HPV-negative tumor, as determined by: negative p16 status, real time PCR or in-situ hybridization. Central confirmation is not required prior to randomization. Equivocal/uncertain HPV status will be allowed on trial.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiationAlso: Chemotherapy, if requiredStandard of Care: Radiation +/- Chemotherapy | Radiation | Arm 1, Radiation +/- Chemotherapy |
| Trans-Oral Surgery (TOS) + Neck DissectionAlso: Radiation, if requiredTrans-Oral Surgery (TOS) + Neck Dissection (plus radiation, if required) | Procedure or surgery | Arm 2, TOS + Neck Dissection |
Primary outcome
Disease-Specific Survival
Time frame: 5 years
Time from randomization to death from cancer
14 secondary outcomes
Overall Survival
Time frame: 5 years
Progression-Free Survival
Time frame: 5 years
Local-Regional Failure
Time frame: 5 years
Distant Failure
Time frame: 5 years
Any Failure
Time frame: 5 years
Quality of Life
Time frame: Baseline to 5 years follow up
Quality of Life
Time frame: Baseline to 5 years follow up
Quality of Life
Time frame: Baseline to 5 years follow up
Quality of Life
Time frame: Baseline to 5 years follow up
Quality of Life
Time frame: Baseline to 5 years follow up
Quality of Life
Time frame: 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
Feeding tube rate at 1 year
Time frame: Baseline to 1 year post treatment
CTCAE Dysphagia Grade
Time frame: Baseline to 5 years post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Danielle MacNeil, M.D. principal investigator
London Regional Cancer Program, London Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation and Trans-Oral Surgery (TOS) + Neck Dissection in people with Head and Neck Cancer and Oropharyngeal Squamous Cell Carcinoma, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
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 11 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: looking for participants now, as of the sponsor's last update on 4 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Susan Archer (519-685-8618, susan.archer@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-Specific Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Sep 2020.