Head and Neck Squamous Cell CarcinomaPhase 2SUPERIORNCT06578871
Surgery and Reducing Ionizing Radiation of the Unknown Primary
A Phase 2 study testing Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk, Surgical Intervention and Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck in people with Head and Neck Squamous Cell Carcinoma and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 3 sites in 2 countries.
Trial summary
About 3% of people with head and neck cancer have cancer in their lymph nodes, but doctors are unable to find the primary tumour. This situation has become more common due to human papillomavirus (HPV), a virus linked to certain cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma, HPV Positive Oropharyngeal Squamous Cell Carcinoma
- What is being tested?
- Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk, Surgical Intervention and Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Jan 2025to 30 May 2027
- 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
- p16 positive PUK SCC of the neck
- Age 18 years or older
- Willing to provide informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Clinical nodal stage N1, AJCC 8th edition (i.e. clinical unilateral nodal disease, none larger than 6 cm)
- Complete clinical work-up, including CT neck, physical examination with nasopharyngoscopy, and PET/CT, with no evidence of a primary tumor. The PET/CT scan must be without focal metabolic activity concerning for a primary tumor, in the opinion of the nuclear medicine physician. Metabolic activity, particularly in the tonsils and base of the tongue which is within normal physiologic range, does not exclude participation.
Show all 9Show fewer
- Completed ipsilateral tonsillectomy and base of tongue mucosectomy with no evidence of a primary tumor
- o Note, patients who had a PET/CT that was initially positive, and therefore not meeting criteria in 4.10, but panendoscopy with biopsies of the fluorodeoxyglucose (FDG)-avid areas do not show malignancy, can then be enrolled and would be returned the OR for a neck dissection prior to randomization
- Ipsilateral nodal disease on pathology with no evidence of extranodal extension
Who cannot join
- Radiological or pathological extra-nodal extension
- Epstein-Barr Virus (EBV)-positive
- Clinical nodal stage (i.e. before neck dissection) N2-3, AJCC 8th edition (ie. bilateral nodes or node >6cm)
- Pathological nodal stage (i.e. after neck dissection) pN3
- Prior history of head and neck cancer within 2 years
- Any other active invasive malignancy, except non-melanotic skin cancers, low-risk prostate cancer, and stage I-IVA papillary or follicular thyroid cancer
Show all 9Show fewer
- Known metastatic disease
- Unable to complete QOL questionnaires
- Pregnant or lactating women
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Australia2 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Jake Jerivs-Bardy, +1670740000, jake.jervis-bardy@sa.gov.au
Jake Jervis-Bardy
Flinders Medical Centre
Adelaide, South Australia, 5042
Jake Jervis-Bardy, +6182045511
Jake Jervis-Bardy
Canada1 site
London Health Sciences Centre
London, Ontario, N6A 5W9
Adrian Mendez, MD, 5196858058, adrian.mendez@lhsc.on.ca
About this study
Official title: Surgery for the Unknown Primary in the Era of p16-positive Oropharyngeal Squamous Cell Carcinoma: Reducing Ionizing Radiation (SUPERIOR): A Randomized Trial
About 3% of people with head and neck cancer have cancer in their lymph nodes, but doctors are unable to find the primary tumour. This situation has become more common due to human papillomavirus (HPV), a virus linked to certain cancers. Generally, patients with HPV-related cancers have a good outlook, with around 90% surviving for at least five years.
Recent advancements in medical technology, such as advanced imaging and specialized surgeries, have significantly improved doctors' ability to find these hidden tumours. These techniques can locate the primary tumour in 70-80% of cases. If the tumour remains undetected, it could be very small or potentially eliminated by the body's immune system.
Read more
The best way to treat this type of cancer is still debated. Current treatment options include surgery to remove lymph nodes or radiation therapy. There is no clear agreement on which areas should receive radiation. Often, surgery is performed on one side of the throat to try and locate the tumour's origin.
Researchers are exploring ways to minimize the harmful side effects of treatment. Some studies suggest that surgery alone might be sufficient for patients with small tumours in their neck, but more research is needed. Another important question is whether radiation needs to cover the entire throat area. Recent findings suggest that omitting radiation from some areas might reduce side effects such as difficulty swallowing and dry mouth.
The SUPERIOR trial aims to investigate whether reducing the amount of radiation can still be effective and improve patients' quality of life. The study also examines whether surgery alone is adequate for certain patients with HPV-related cancers.
Read the detailed description
Approximately 3% of all head and neck squamous cell carcinoma (SCC) patients present with nodal disease from an unknown primary (PUK). The incidence of PUK has increased in tandem with the rise of human papillomavirus (HPV)-mediated oropharyngeal SCC (OPSCC). HPV-mediated PUK now represents at least half of the head and neck PUK population, with an excellent prognosis and approximately 90% 5-year overall survival (OS).
The work-up for PUK has significantly improved with the introduction of positron emission tomography (PET) imaging and transoral robotic surgery (TORS). PET identifies at least 40% of primaries in PUK patients when clinical and radiological work-up is negative, and TORS has a higher primary identification rate (70%-80%). Current guidelines recommend tonsillectomy and tongue base mucosectomy in the work-up of PUK patients.
Definitive management of HPV-mediated PUK remains controversial, with curative options including primary neck dissection ± adjuvant therapy or primary radiotherapy ± concurrent chemotherapy. Treatment morbidity is significant, despite the excellent outcomes (90% 5-year OS). Key issues include the choice of initial treatment modality and whether to treat mucosal surfaces with radiation prophylactically.
Current guidelines recommend single-modality surgery (neck dissection) for low-volume neck disease. This recommendation is based on studies suggesting low primary emergence rates (1.5%-7%) and outcomes comparable to non-surgical treatment paradigms. Evidence from early-stage OPSCC supports surgery alone as a safe option for HPV-mediated PUK.
A critical question is whether to irradiate mucosal surfaces when using radiotherapy for HPV-mediated PUK. Emerging data suggest that omitting mucosal radiation has a very low risk (<5%) of primary tumour emergence, potentially improving long-term quality of life and reducing toxicities like dysphagia and xerostomia. Several retrospective studies support the safety and reduced toxicity of involved neck radiotherapy without mucosal irradiation.
This trial is specifically designed with an upfront neck dissection alongside tonsillectomy and tongue base mucosectomy. Combining an upfront therapeutic neck dissection with the final stage of the diagnostic work-up has several benefits. Surgically treating the neck in selected patients during tonsillectomy and tongue base mucosectomy accelerates treatment, avoids additional delays, reduces costs to healthcare institutions, and prevents the need for a second surgery if no primary is identified. The addition of neck dissection to tonsillectomy and tongue base mucosectomy also involves relatively minor additional surgical morbidity in the context of a patient already undergoing pharyngeal surgery. In some instances, upfront surgical treatment of the neck may complete definitive treatment at the earliest opportunity. Patients with intermediate-volume neck disease, who require dual-modality treatment, also benefit from no further surgical delay and can proceed to radiotherapy following a single surgical encounter. An upfront neck dissection is also the gold standard for lymph node evaluation and may down-stage patients into a unimodality approach, thereby avoiding additional toxicity. For example, if imaging suggests multiple involved ipsilateral nodes in an HPV-mediated PUK patient, conventional treatment would involve dual-modality therapy. Pathological staging may down-stage this patient into a unimodality paradigm, sparing them significant toxicity.
In this randomized phase II trial, the study team hypothesizes that omitting mucosal radiation will lead to improved quality of life, decreased toxicity, and low rates of primary tumour emergence. Further, the researchers hypothesize that neck dissection alone for low-volume HPV-mediated PUK will result in excellent oncologic and functional outcomes.
The main objective is to assess the impact of omitting mucosal radiation on oncologic outcomes, toxicity, functional outcomes, and quality of life (QOL) in patients with p16-positive PUK.
The primary endpoint is to determine the rate of primary emergence of a mucosal p16-positive SCC in the upper aerodigestive tract compared to historical controls.
The secondary endpoints include:
Quality of life (using MDADI, EORTC QLQ-C30 and H\&N35, EQ-5D-5L, NDII) Overall survival (OS) Disease-free survival Regional recurrence within the neck Distant recurrence outside the upper aerodigestive tract and neck levels Rate of salvage treatment for primary emergence Rate of unsalvageable primary emergence Rate of percutaneous feeding tube insertion and use at 1 year Swallowing function (DIGEST score, FOIS) Toxicity (CTCAE version 5) Patients will be randomized 1:2 between the standard of care (Arm 1) and omission of radiation to mucosal surfaces (Arm 2).
Combining neck dissection with tonsillectomy and tongue base mucosectomy accelerates treatment, reduces costs, and avoids additional surgery. This approach involves minor additional surgical morbidity and can complete definitive treatment at the earliest opportunity. Upfront neck dissection also allows for accurate lymph node evaluation and potential down-staging, thereby sparing patients from additional toxicity.
The SUPERIOR trial aims to determine whether omitting mucosal radiation improves quality of life and reduces toxicity in HPV-mediated PUK patients, while evaluating the efficacy of neck dissection alone for low-volume disease. The study seeks to establish evidence-based guidelines for the optimal management of HPV-mediated PUK.
- Being tested
- Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk, Surgical Intervention, Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck
- Keywords
- HPV-Mediated PUK, Head and Neck Cancer, P16+, Radiation Therapy, Oropharyngeal Cancer, Squamous Cell Carcinoma, Transoral Robotic Surgery (TORS), Mucosal Radiation, SUPERIOR Trial
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Oropharyngeal Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensity Modulated Radiotherapy (IMRT) to Mucosa at RiskRadiation
Patients in Arm 1, after the surgical procedure, will receive radiotherapy to the at-risk mucosa.
Surgical InterventionProcedure or surgery
These patients will undergo Neck dissection, TORS tonsillectomy (unilateral vs bilateral tonsillectomy at the discretion of the treating physician) + ipsilateral tongue base mucosectomy.
Intensity Modulated Radiotherapy (IMRT) to Ipsilateral NeckRadiation
For Arm1, after the surgical procedure, the patients will receive radiotherapy to the ipsilateral neck. For Arm2, the patients will only receive IMRT to neck, if multiple ipsilateral nodes or single ipsilateral node >3 cm is observed
| Study group | Role | What they receive |
|---|---|---|
| Arm1: Standard of Care Treatment | Active comparator | Radiotherapy to Ipsilateral Neck and to risk Mucosa
There are two possible dose levels:
* 60 Gy in 30 fractions over 6 weeks (CTV60)
o This applies to the dissected levels of the neck
* 54 Gy in 30 fractions over 6 weeks (CTV54)
* This applies to the mucosal surfaces. Patients randomized to Arm 2 will not have the mucosal surfaces treated Receives: Radiation: Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk; Procedure: Surgical Intervention; Radiation: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck |
| Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck | Experimental | * If N1 with single node <= 3cm, no further treatment
* If multiple ipsilateral nodes or single ipsilateral node >3 cm, radiation to Neck only Receives: Procedure: Surgical Intervention; Radiation: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Endpoint: Rate of Primary Emergence of Mucosal p16-Positive Squamous Cell Carcinoma
The primary endpoint of this clinical trial is to assess the rate at which a primary mucosal p16-positive squamous cell carcinoma (SCC) emerges in the upper aerodigestive tract (which includes the oral cavity, pharynx, or larynx) in patients with p16-positive PUK of the head and neck. This rate will be compared to a historical control to determine the impact of omitting mucosal radiation in these patients. The primary objective is to evaluate the oncologic outcomes associated with this treatment approach.
Measured: 2 years
Secondary outcomes (15)
MD Anderson Dysphagia Inventory (MDADI)
MD Anderson Dysphagia Inventory (MDADI): Measures the impact of swallowing difficulties on a patient's daily life and emotional well-being.
Scale Range: 20 to 100. Interpretation: Higher scores indicate a better outcome, reflecting better swallowing function and less impact on quality of life.
Measured: Assessed at baseline, 6 months, and 1 year post randomization
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Outcome Measure: General health status and overall quality of life in cancer patients, including physical functioning, role functioning, emotional functioning, and overall health.
Scale Range: 0 to 100.
Interpretation: Higher scores on functional scales and global health status indicate a better outcome. Higher scores on symptom scales indicate a worse outcome.
Measured: Time Frame: Assessed at baseline, 6 months, and 1 year post randomization.
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-H&N35)
Outcome Measure: Head and neck cancer-specific symptoms and issues, particularly related to treatment effects.
Scale Range: 0 to 100. Interpretation: Higher scores on symptom scales indicate a worse outcome, reflecting more severe symptoms or problems related to head and neck cancer.
Measured: Assessed at baseline, 6 months, and 1 year post randomization
European Quality of life (Euro-QoL) 5-Dimension 5-Level (EQ-5D-5L): Visual Analog Scale
Outcome Measure: Health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Scale Range: -0.281 to 1 (Index value) and 0 to 100 (Visual Analog Scale).
Interpretation: For the Index value, higher scores indicate a better outcome (better health-related quality of life). For the Visual Analog Scale, higher scores indicate better perceived overall health.
Measured: Assessed at baseline, 6 months, and 1 year post randomization
Neck Dissection Impairment Index (NDII):
Outcome Measure: Specific impairments related to neck dissection, including physical and functional issues in the neck area.
Scale Range: 0 to 100.
Interpretation: Higher scores indicate a better outcome, reflecting fewer impairments and better neck function.
Measured: Assessed at baseline, 6 months, and 1 year post randomization
Overall Survival
Overall Survival (OS): Defined as the time from randomization until death or the last follow-up, whichever occurs first.
Measured: From the date of randomization until the date of death from any cause, assessed for a minimum of five years.
Disease Free Survival
The time from randomization until the first occurrence of disease recurrence, death, or the last follow-up, whichever comes first.
Measured: From the date of randomization until the date of first documented disease recurrence or progression, or death from any cause, whichever occurs first, assessed for a minimum of five years.
Regional Recurrence
The occurrence of recurrent cancer specifically within the nodal levels of the neck (levels I-VI).
Measured: From the date of randomization until the date of first documented regional recurrence or until date of death from any cause, assessed throughout the study with a minimum follow-up of five years.
Distant Recurrence
The development of recurrent cancer outside the upper aerodigestive tract and neck levels.
Measured: From the date of randomization until the date of first documented distant recurrence or until date of death from any cause, assessed throughout the study with a minimum follow-up of five years.
Rate of Salvage Treatment for Primary Emergence
The frequency of additional treatments (surgery ± radiotherapy) required for the emergence of a p16-positive primary mucosal tumour, with the intent of cure.
Measured: Assessed throughout the study, with follow-up for at least 5 years from randomization.
Rate of Unsalvageable Primary Emergence
The frequency of emergence of a p16-positive primary mucosal tumour that cannot be treated with surgery or radiotherapy with the intent of cure.
Measured: From the date of randomization until the initiation of salvage treatment for primary emergence, assessed throughout the study with a minimum follow-up of five years.
Rate of Percutaneous Feeding Tube Insertion and Use
The frequency of percutaneous feeding tube insertion and the rate of feeding tube use 1 year after randomization.
Measured: From the date of randomization through one year, with follow-up assessments at one year. Percutaneous feeding tube insertion and use will be recorded throughout this period.
Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) score
Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) score: Measures the severity of swallowing dysfunction particularly related to the impact of cancer treatment on swallowing ability. It evaluates changes in swallowing function as seen through imaging techniques, such as fluoroscopy or videofluoroscopy.
Scale Used: Typically, the DIGEST score is a categorical scale with grades ranging from 0 to 4.
Lower Scores: Indicate less severe swallowing dysfunction or no dysfunction. Higher Scores: Indicate more severe swallowing dysfunction, with a greater impact on the ability to eat and drink.
Measured: From the date of randomization, with swallowing function assessed at one year post-randomization.
Functional Oral Intake Score (FOIS)
Functional Oral Intake Score (FOIS): Assesses the ability to consume food and liquids by mouth. It assesses how much and what type of food and liquids a patient can safely consume.
Scale Used: The FOIS is a categorical scale with grades ranging from 1 to 7.
Lower Scores: Indicate greater dependence on non-oral feeding methods or more restricted oral intake.
Higher Scores: Indicate greater ability to consume a wide variety of foods and liquids by mouth, with fewer restrictions.
Measured: From the date of randomization, with swallowing function assessed at one year post-randomization.
Toxicity : Assessment of Treatment-Related Adverse Events Using CTCAE v5.0
Toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, which categorizes the severity and type of adverse effects experienced by patients.
The assessment focuses on:
Severity of Adverse Events: Evaluate the intensity of side effects related to treatment, ranging from mild to severe.
Type of Adverse Events: Identifies specific side effects, such as nausea, fatigue, pain, and other treatment-related symptoms.
Frequency and Duration: Monitors how often and for how long patients experience these adverse effects.
Measured: Toxicity will be monitored throughout the study, with evaluations at regular intervals up to 1 year or until date of death, whichever comes first, post-randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2024
- Study start1 Jan 2025 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies 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
- This is a randomized phase II study. Patients will be randomized between current standard of care treatment (Arm 1) vs. omission of radiation mucosal surfaces (Arm 2) in a 1:2 ratio.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 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
- Collaborators
- Dr. Jake Jervis-Bardy, Dr. David Palma, Dr. Adam Mutsaers
- Responsible party
- Principal investigator, Adrian Mendez, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Adrian I Mendez, MD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sJake Jervis-Bardy, MD, Principal investigator, Royal Adelaide Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06578871
- Sponsor's protocol ID
- 15080
- Other IDs
- 5007
- Acronym
- SUPERIOR
- Status last verified
- Aug 2024
- First submitted
- 14 Aug 2024
- Last updated
- 3 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: In line with our commitment to transparency and scientific progress, we will share our study protocol, statistical analysis plan, and participant consent forms with the broader research community after receiving Research Ethics Board (REB) approval. Study Protocol: Details the trial's objectives, design, methodology, and operational aspects, including participant criteria, interventions, and outcomes. Statistical Analysis Plan: Outlines the methods and statistical techniques for analyzing trial data. Participant Consent Forms: Follow OCREB guidelines, detailing study risks, benefits, and participants' rights, ensuring transparency in the consent process. These documents will be available on ClinicalTrials.gov. Researchers can request access by contacting Dr. Adrian Mendez at adrian.mendez@lhsc.on.ca or Halema Khan at halema.khan@lhsc.on.ca.
Publications
Ryan JF, Motz KM, Rooper LM, Mydlarz WK, Quon H, Gourin CG, Tan M, Eisele DW, Fakhry C. The Impact of a Stepwise Approach to Primary Tumor Detection in Squamous Cell Carcinoma of the Neck With Unknown Primary. Laryngoscope. 2019 Jul;129(7):1610-1616. doi: 10.1002/lary.27625. Epub 2018 Nov 22.
PubMed 30565698Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec 20;31(36):4550-9. doi: 10.1200/JCO.2013.50.3870. Epub 2013 Nov 18.
PubMed 24248688Ren J, Yang W, Su J, Ren X, Fazelzad R, Albert T, Habbous S, Goldstein DP, de Almeida JR, Hansen A, Jang R, Bratman SV, Hope A, Chen R, Wang J, Xu Y, Cheng D, Zhao Y, Xu W, Liu G. Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region. Int J Cancer. 2019 Sep 15;145(6):1465-1474. doi: 10.1002/ijc.32164. Epub 2019 Feb 19.
PubMed 30698281Chen B, Zhang H, Liu D, Wang X, Ji B, Gao S. Diagnostic performance of 18F-FDG PET/CT for the detection of occult primary tumors in squamous cell carcinoma of unknown primary in the head and neck: a single-center retrospective study. Nucl Med Commun. 2021 May 1;42(5):523-527. doi: 10.1097/MNM.0000000000001365.
PubMed 33481505Farooq S, Khandavilli S, Dretzke J, Moore D, Nankivell PC, Sharma N, Almeida JR, Winter SC, Simon C, Paleri V, De M, Siddiq S, Holsinger C, Ferris RL, Mehanna H. Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis. Oral Oncol. 2019 Apr;91:97-106. doi: 10.1016/j.oraloncology.2019.02.018. Epub 2019 Mar 6.
PubMed 30926070Maghami E, Ismaila N, Alvarez A, Chernock R, Duvvuri U, Geiger J, Gross N, Haughey B, Paul D, Rodriguez C, Sher D, Stambuk HE, Waldron J, Witek M, Caudell J. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline. J Clin Oncol. 2020 Aug 1;38(22):2570-2596. doi: 10.1200/JCO.20.00275. Epub 2020 Apr 23.
PubMed 32324430Ferris RL, Flamand Y, Weinstein GS, Li S, Quon H, Mehra R, Garcia JJ, Chung CH, Gillison ML, Duvvuri U, O'Malley BW Jr, Ozer E, Thomas GR, Koch WM, Gross ND, Bell RB, Saba NF, Lango M, Mendez E, Burtness B. Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol. 2022 Jan 10;40(2):138-149. doi: 10.1200/JCO.21.01752. Epub 2021 Oct 26.
PubMed 34699271Chen AM. De-Escalation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer: Questions for Practical Consideration. Oncology (Williston Park). 2023 Jul 21;37(7):281-287. doi: 10.46883/2023.25921000.
PubMed 37499250Sivars L, Nasman A, Tertipis N, Vlastos A, Ramqvist T, Dalianis T, Munck-Wikland E, Nordemar S. Human papillomavirus and p53 expression in cancer of unknown primary in the head and neck region in relation to clinical outcome. Cancer Med. 2014 Apr;3(2):376-84. doi: 10.1002/cam4.199. Epub 2014 Feb 10.
PubMed 24510528Mackenzie K, Watson M, Jankowska P, Bhide S, Simo R. Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016 May;130(S2):S170-S175. doi: 10.1017/S0022215116000591.
PubMed 27841129Network NCC. 2023. NCCN clinical practice guidelines in oncology: head and neck cancers. Fort Washington, PA, nd.
Axelsson L, Nyman J, Haugen-Cange H, Bove M, Johansson L, De Lara S, Kovacs A, Hammerlid E. Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection. J Otolaryngol Head Neck Surg. 2017 Jun 10;46(1):45. doi: 10.1186/s40463-017-0223-1.
PubMed 28601094Wichmann G, Willner M, Kuhnt T, Kluge R, Gradistanac T, Wald T, Fest S, Lordick F, Dietz A, Wiegand S, Zebralla V. Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients. Front Oncol. 2021 May 7;11:682088. doi: 10.3389/fonc.2021.682088. eCollection 2021.
PubMed 34026656Zhou MJ, van Zante A, Lazar AA, Groppo ER, Garsa AA, Ryan WR, El-Sayed IH, Eisele DW, Yom SS. Squamous cell carcinoma of unknown primary of the head and neck: Favorable prognostic factors comparable to those in oropharyngeal cancer. Head Neck. 2018 May;40(5):904-916. doi: 10.1002/hed.25028. Epub 2017 Dec 6.
PubMed 29210145Takhar A, Wilkie MD, Srinivasan D, King E. Head and Neck Squamous Cell Carcinoma of Unknown Primary-Who Can Be Offered Surgery as the Sole Treatment Modality? A Systematic Review. Clin Otolaryngol. 2025 May;50(3):399-414. doi: 10.1111/coa.14279. Epub 2025 Jan 12.
PubMed 39800989
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgery for the Unknown Primary in the Era of p16-positive Oropharyngeal Squamous Cell Carcinoma: Reducing Ionizing Radiation (SUPERIOR): A Randomized Trial
- ClinicalTrials.gov ID
- NCT06578871
- Acronym / sponsor ID
- SUPERIOR / 15080
- Keywords
- HPV-Mediated PUK, Head and Neck Cancer, P16+, Radiation Therapy, Oropharyngeal Cancer, Squamous Cell Carcinoma, Transoral Robotic Surgery (TORS), Mucosal Radiation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- Dr. Jake Jervis-Bardy, Dr. David Palma, Dr. Adam Mutsaers
- Study start
- 1 Jan 2025 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 29 Aug 2024 (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.
About 3% of people with head and neck cancer have cancer in their lymph nodes, but doctors are unable to find the primary tumour. This situation has become more common due to human papillomavirus (HPV), a virus linked to certain cancers. Generally, patients with HPV-related cancers have a good outlook, with around 90% surviving for at least five years.
Recent advancements in medical technology, such as advanced imaging and specialized surgeries, have significantly improved doctors' ability to find these hidden tumours. These techniques can locate the primary tumour in 70-80% of cases. If the tumour remains undetected, it could be very small or potentially eliminated by the body's immune system.
The best way to treat this type of cancer is still debated. Current treatment options include surgery to remove lymph nodes or radiation therapy. There is no clear agreement on which areas should receive radiation. Often, surgery is performed on one side of the throat to try and locate the tumour's origin.
Researchers are exploring ways to minimize the harmful side effects of treatment. Some studies suggest that surgery alone might be sufficient for patients with small tumours in their neck, but more research is needed. Another important question is whether radiation needs to cover the entire throat area. Recent findings suggest that omitting radiation from some areas might reduce side effects such as difficulty swallowing and dry mouth.
The SUPERIOR trial aims to investigate whether reducing the amount of radiation can still be effective and improve patients' quality of life. The study also examines whether surgery alone is adequate for certain patients with HPV-related cancers.
Detailed description
Approximately 3% of all head and neck squamous cell carcinoma (SCC) patients present with nodal disease from an unknown primary (PUK). The incidence of PUK has increased in tandem with the rise of human papillomavirus (HPV)-mediated oropharyngeal SCC (OPSCC). HPV-mediated PUK now represents at least half of the head and neck PUK population, with an excellent prognosis and approximately 90% 5-year overall survival (OS).
The work-up for PUK has significantly improved with the introduction of positron emission tomography (PET) imaging and transoral robotic surgery (TORS). PET identifies at least 40% of primaries in PUK patients when clinical and radiological work-up is negative, and TORS has a higher primary identification rate (70%-80%). Current guidelines recommend tonsillectomy and tongue base mucosectomy in the work-up of PUK patients.
Definitive management of HPV-mediated PUK remains controversial, with curative options including primary neck dissection ± adjuvant therapy or primary radiotherapy ± concurrent chemotherapy. Treatment morbidity is significant, despite the excellent outcomes (90% 5-year OS). Key issues include the choice of initial treatment modality and whether to treat mucosal surfaces with radiation prophylactically.
Current guidelines recommend single-modality surgery (neck dissection) for low-volume neck disease. This recommendation is based on studies suggesting low primary emergence rates (1.5%-7%) and outcomes comparable to non-surgical treatment paradigms. Evidence from early-stage OPSCC supports surgery alone as a safe option for HPV-mediated PUK.
A critical question is whether to irradiate mucosal surfaces when using radiotherapy for HPV-mediated PUK. Emerging data suggest that omitting mucosal radiation has a very low risk (<5%) of primary tumour emergence, potentially improving long-term quality of life and reducing toxicities like dysphagia and xerostomia. Several retrospective studies support the safety and reduced toxicity of involved neck radiotherapy without mucosal irradiation.
This trial is specifically designed with an upfront neck dissection alongside tonsillectomy and tongue base mucosectomy. Combining an upfront therapeutic neck dissection with the final stage of the diagnostic work-up has several benefits. Surgically treating the neck in selected patients during tonsillectomy and tongue base mucosectomy accelerates treatment, avoids additional delays, reduces costs to healthcare institutions, and prevents the need for a second surgery if no primary is identified. The addition of neck dissection to tonsillectomy and tongue base mucosectomy also involves relatively minor additional surgical morbidity in the context of a patient already undergoing pharyngeal surgery. In some instances, upfront surgical treatment of the neck may complete definitive treatment at the earliest opportunity. Patients with intermediate-volume neck disease, who require dual-modality treatment, also benefit from no further surgical delay and can proceed to radiotherapy following a single surgical encounter. An upfront neck dissection is also the gold standard for lymph node evaluation and may down-stage patients into a unimodality approach, thereby avoiding additional toxicity. For example, if imaging suggests multiple involved ipsilateral nodes in an HPV-mediated PUK patient, conventional treatment would involve dual-modality therapy. Pathological staging may down-stage this patient into a unimodality paradigm, sparing them significant toxicity.
In this randomized phase II trial, the study team hypothesizes that omitting mucosal radiation will lead to improved quality of life, decreased toxicity, and low rates of primary tumour emergence. Further, the researchers hypothesize that neck dissection alone for low-volume HPV-mediated PUK will result in excellent oncologic and functional outcomes.
The main objective is to assess the impact of omitting mucosal radiation on oncologic outcomes, toxicity, functional outcomes, and quality of life (QOL) in patients with p16-positive PUK.
The primary endpoint is to determine the rate of primary emergence of a mucosal p16-positive SCC in the upper aerodigestive tract compared to historical controls.
The secondary endpoints include:
Quality of life (using MDADI, EORTC QLQ-C30 and H\&N35, EQ-5D-5L, NDII) Overall survival (OS) Disease-free survival Regional recurrence within the neck Distant recurrence outside the upper aerodigestive tract and neck levels Rate of salvage treatment for primary emergence Rate of unsalvageable primary emergence Rate of percutaneous feeding tube insertion and use at 1 year Swallowing function (DIGEST score, FOIS) Toxicity (CTCAE version 5) Patients will be randomized 1:2 between the standard of care (Arm 1) and omission of radiation to mucosal surfaces (Arm 2).
Combining neck dissection with tonsillectomy and tongue base mucosectomy accelerates treatment, reduces costs, and avoids additional surgery. This approach involves minor additional surgical morbidity and can complete definitive treatment at the earliest opportunity. Upfront neck dissection also allows for accurate lymph node evaluation and potential down-staging, thereby sparing patients from additional toxicity.
The SUPERIOR trial aims to determine whether omitting mucosal radiation improves quality of life and reduces toxicity in HPV-mediated PUK patients, while evaluating the efficacy of neck dissection alone for low-volume disease. The study seeks to establish evidence-based guidelines for the optimal management of HPV-mediated PUK.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized phase II study. Patients will be randomized between current standard of care treatment (Arm 1) vs. omission of radiation mucosal surfaces (Arm 2) in a 1:2 ratio.
| Arm | Type | Receives |
|---|---|---|
| Arm1: Standard of Care Treatment | Active comparator | Radiation: Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk, Procedure: Surgical Intervention, Radiation: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral NeckRadiotherapy to Ipsilateral Neck and to risk Mucosa There are two possible dose levels: * 60 Gy in 30 fractions over 6 weeks (CTV60) o This applies to the dissected levels of the neck * 54 Gy in 30 fractions over 6 weeks (CTV54) * This applies to the mucosal surfaces. Patients randomized to Arm 2 will not have the mucosal surfaces treated |
| Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck | Experimental | Procedure: Surgical Intervention, Radiation: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck* If N1 with single node <= 3cm, no further treatment * If multiple ipsilateral nodes or single ipsilateral node >3 cm, radiation to Neck only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- p16 positive PUK SCC of the neck
- Age 18 years or older
- Willing to provide informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Clinical nodal stage N1, AJCC 8th edition (i.e. clinical unilateral nodal disease, none larger than 6 cm)
Key exclusion criteria (9 listed)
- Radiological or pathological extra-nodal extension
- Epstein-Barr Virus (EBV)-positive
- Clinical nodal stage (i.e. before neck dissection) N2-3, AJCC 8th edition (ie. bilateral nodes or node >6cm)
- Pathological nodal stage (i.e. after neck dissection) pN3
- Prior history of head and neck cancer within 2 years
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 |
|---|---|---|
| Intensity Modulated Radiotherapy (IMRT) to Mucosa at RiskPatients in Arm 1, after the surgical procedure, will receive radiotherapy to the at-risk mucosa. | Radiation | Arm1: Standard of Care Treatment |
| Surgical InterventionThese patients will undergo Neck dissection, TORS tonsillectomy (unilateral vs bilateral tonsillectomy at the discretion of the treating physician) + ipsilateral tongue base mucosectomy. | Procedure or surgery | Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck, Arm1: Standard of Care Treatment |
| Intensity Modulated Radiotherapy (IMRT) to Ipsilateral NeckFor Arm1, after the surgical procedure, the patients will receive radiotherapy to the ipsilateral neck. For Arm2, the patients will only receive IMRT to neck, if multiple ipsilateral nodes or single ipsilateral node >3 cm is observed | Radiation | Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck, Arm1: Standard of Care Treatment |
Primary outcome
Primary Endpoint: Rate of Primary Emergence of Mucosal p16-Positive Squamous Cell Carcinoma
Time frame: 2 years
The primary endpoint of this clinical trial is to assess the rate at which a primary mucosal p16-positive squamous cell carcinoma (SCC) emerges in the upper aerodigestive tract (which includes the oral cavity, pharynx, or larynx) in patients with p16-positive PUK of the head and neck. This rate will be compared to a historical control to determine the impact of omitting mucosal radiation in these patients. The primary objective is to evaluate the oncologic outcomes associated with this treatment approach.
15 secondary outcomes
MD Anderson Dysphagia Inventory (MDADI)
Time frame: Assessed at baseline, 6 months, and 1 year post randomization
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: Time Frame: Assessed at baseline, 6 months, and 1 year post randomization.
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-H&N35)
Time frame: Assessed at baseline, 6 months, and 1 year post randomization
European Quality of life (Euro-QoL) 5-Dimension 5-Level (EQ-5D-5L): Visual Analog Scale
Time frame: Assessed at baseline, 6 months, and 1 year post randomization
Neck Dissection Impairment Index (NDII):
Time frame: Assessed at baseline, 6 months, and 1 year post randomization
Overall Survival
Time frame: From the date of randomization until the date of death from any cause, assessed for a minimum of five years.
Disease Free Survival
Time frame: From the date of randomization until the date of first documented disease recurrence or progression, or death from any cause, whichever occurs first, assessed for a minimum of five years.
Regional Recurrence
Time frame: From the date of randomization until the date of first documented regional recurrence or until date of death from any cause, assessed throughout the study with a minimum follow-up of five years.
Distant Recurrence
Time frame: From the date of randomization until the date of first documented distant recurrence or until date of death from any cause, assessed throughout the study with a minimum follow-up of five years.
Rate of Salvage Treatment for Primary Emergence
Time frame: Assessed throughout the study, with follow-up for at least 5 years from randomization.
Rate of Unsalvageable Primary Emergence
Time frame: From the date of randomization until the initiation of salvage treatment for primary emergence, assessed throughout the study with a minimum follow-up of five years.
Rate of Percutaneous Feeding Tube Insertion and Use
Time frame: From the date of randomization through one year, with follow-up assessments at one year. Percutaneous feeding tube insertion and use will be recorded throughout this period.
Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) score
Time frame: From the date of randomization, with swallowing function assessed at one year post-randomization.
Functional Oral Intake Score (FOIS)
Time frame: From the date of randomization, with swallowing function assessed at one year post-randomization.
Toxicity : Assessment of Treatment-Related Adverse Events Using CTCAE v5.0
Time frame: Toxicity will be monitored throughout the study, with evaluations at regular intervals up to 1 year or until date of death, whichever comes first, post-randomization.
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 3 Sep 2024.
- Background: PubMed 30565698Ryan JF, Motz KM, Rooper LM, Mydlarz WK, Quon H, Gourin CG, Tan M, Eisele DW, Fakhry C. The Impact of a Stepwise Approach to Primary Tumor Detection in Squamous Cell Carcinoma of the Neck With Unknown Primary. Laryngoscope. 2019 Jul;129(7):1610-1616. doi: 10.1002/lary.27625. Epub 2018 Nov 22.
- Background: PubMed 24248688Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec 20;31(36):4550-9. doi: 10.1200/JCO.2013.50.3870. Epub 2013 Nov 18.
- Background: PubMed 30698281Ren J, Yang W, Su J, Ren X, Fazelzad R, Albert T, Habbous S, Goldstein DP, de Almeida JR, Hansen A, Jang R, Bratman SV, Hope A, Chen R, Wang J, Xu Y, Cheng D, Zhao Y, Xu W, Liu G. Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region. Int J Cancer. 2019 Sep 15;145(6):1465-1474. doi: 10.1002/ijc.32164. Epub 2019 Feb 19.
- Background: PubMed 33481505Chen B, Zhang H, Liu D, Wang X, Ji B, Gao S. Diagnostic performance of 18F-FDG PET/CT for the detection of occult primary tumors in squamous cell carcinoma of unknown primary in the head and neck: a single-center retrospective study. Nucl Med Commun. 2021 May 1;42(5):523-527. doi: 10.1097/MNM.0000000000001365.
- Background: PubMed 30926070Farooq S, Khandavilli S, Dretzke J, Moore D, Nankivell PC, Sharma N, Almeida JR, Winter SC, Simon C, Paleri V, De M, Siddiq S, Holsinger C, Ferris RL, Mehanna H. Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis. Oral Oncol. 2019 Apr;91:97-106. doi: 10.1016/j.oraloncology.2019.02.018. Epub 2019 Mar 6.
- Background: PubMed 32324430Maghami E, Ismaila N, Alvarez A, Chernock R, Duvvuri U, Geiger J, Gross N, Haughey B, Paul D, Rodriguez C, Sher D, Stambuk HE, Waldron J, Witek M, Caudell J. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline. J Clin Oncol. 2020 Aug 1;38(22):2570-2596. doi: 10.1200/JCO.20.00275. Epub 2020 Apr 23.
- Background: PubMed 34699271Ferris RL, Flamand Y, Weinstein GS, Li S, Quon H, Mehra R, Garcia JJ, Chung CH, Gillison ML, Duvvuri U, O'Malley BW Jr, Ozer E, Thomas GR, Koch WM, Gross ND, Bell RB, Saba NF, Lango M, Mendez E, Burtness B. Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol. 2022 Jan 10;40(2):138-149. doi: 10.1200/JCO.21.01752. Epub 2021 Oct 26.
- Background: PubMed 37499250Chen AM. De-Escalation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer: Questions for Practical Consideration. Oncology (Williston Park). 2023 Jul 21;37(7):281-287. doi: 10.46883/2023.25921000.
- Background: PubMed 24510528Sivars L, Nasman A, Tertipis N, Vlastos A, Ramqvist T, Dalianis T, Munck-Wikland E, Nordemar S. Human papillomavirus and p53 expression in cancer of unknown primary in the head and neck region in relation to clinical outcome. Cancer Med. 2014 Apr;3(2):376-84. doi: 10.1002/cam4.199. Epub 2014 Feb 10.
- Background: PubMed 27841129Mackenzie K, Watson M, Jankowska P, Bhide S, Simo R. Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016 May;130(S2):S170-S175. doi: 10.1017/S0022215116000591.
- BackgroundNetwork NCC. 2023. NCCN clinical practice guidelines in oncology: head and neck cancers. Fort Washington, PA, nd.
- Background: PubMed 28601094Axelsson L, Nyman J, Haugen-Cange H, Bove M, Johansson L, De Lara S, Kovacs A, Hammerlid E. Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection. J Otolaryngol Head Neck Surg. 2017 Jun 10;46(1):45. doi: 10.1186/s40463-017-0223-1.
- Individual participant dataSharing planned: Yes. In line with our commitment to transparency and scientific progress, we will share our study protocol, statistical analysis plan, and participant consent forms with the broader research community after receiving Research Ethics Board (REB) approval. Study Protocol: Details the trial's objectives, design, methodology, and operational aspects, including participant criteria, interventions, and outcomes. Statistical Analysis Plan: Outlines the methods and statistical techniques for analyzing trial data. Participant Consent Forms: Follow OCREB guidelines, detailing study risks, benefits, and participants' rights, ensuring transparency in the consent process. These documents will be available on ClinicalTrials.gov. Researchers can request access by contacting Dr. Adrian Mendez at adrian.mendez@lhsc.on.ca or Halema Khan at halema.khan@lhsc.on.ca.
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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.
Adrian I Mendez, MD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Jake Jervis-Bardy, MD principal investigator
Royal Adelaide Hospital
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk, Surgical Intervention and Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck in people with Head and Neck Squamous Cell Carcinoma and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 3 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 9 inclusion and 9 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: opening soon, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia, 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 Halema Khan, PhD (5196858500, halema.khan@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Endpoint: Rate of Primary Emergence of Mucosal p16-Positive Squamous Cell Carcinoma (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 NCT06578871, which also lists 21 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 3 Sep 2024; AzTrials last refreshed its copy on 6 Nov 2026.