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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06578871




Registration number
NCT06578871
Ethics application status
Date submitted
14/08/2024
Date registered
29/08/2024

Titles & IDs
Public title
Surgery and Reducing Ionizing Radiation of the Unknown Primary
Scientific title
Surgery for the Unknown Primary in the Era of p16-positive Oropharyngeal Squamous Cell Carcinoma: Reducing Ionizing Radiation (SUPERIOR): A Randomized Trial
Secondary ID [1] 0 0
5007
Secondary ID [2] 0 0
15080
Universal Trial Number (UTN)
Trial acronym
SUPERIOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Squamous Cell Carcinoma 0 0
HPV Positive Oropharyngeal Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk
Treatment: Surgery - Surgical Intervention
Treatment: Other - Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck

Active comparator: Arm1: Standard of Care Treatment - 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

Experimental: Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck - * If N1 with single node \<= 3cm, no further treatment
* If multiple ipsilateral nodes or single ipsilateral node \>3 cm, radiation to Neck only


Treatment: Other: Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk
Patients in Arm 1, after the surgical procedure, will receive radiotherapy to the at-risk mucosa.

Treatment: Surgery: Surgical Intervention
These patients will undergo Neck dissection, TORS tonsillectomy (unilateral vs bilateral tonsillectomy at the discretion of the treating physician) + ipsilateral tongue base mucosectomy.

Treatment: Other: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck
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
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Endpoint: Rate of Primary Emergence of Mucosal p16-Positive Squamous Cell Carcinoma
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
MD Anderson Dysphagia Inventory (MDADI)
Timepoint [1] 0 0
Assessed at baseline, 6 months, and 1 year post randomization
Secondary outcome [2] 0 0
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Timepoint [2] 0 0
Time Frame: Assessed at baseline, 6 months, and 1 year post randomization.
Secondary outcome [3] 0 0
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-H&N35)
Timepoint [3] 0 0
Assessed at baseline, 6 months, and 1 year post randomization
Secondary outcome [4] 0 0
European Quality of life (Euro-QoL) 5-Dimension 5-Level (EQ-5D-5L): Visual Analog Scale
Timepoint [4] 0 0
Assessed at baseline, 6 months, and 1 year post randomization
Secondary outcome [5] 0 0
Neck Dissection Impairment Index (NDII):
Timepoint [5] 0 0
Assessed at baseline, 6 months, and 1 year post randomization
Secondary outcome [6] 0 0
Overall Survival
Timepoint [6] 0 0
From the date of randomization until the date of death from any cause, assessed for a minimum of five years.
Secondary outcome [7] 0 0
Disease Free Survival
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Regional Recurrence
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
Distant Recurrence
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Rate of Salvage Treatment for Primary Emergence
Timepoint [10] 0 0
Assessed throughout the study, with follow-up for at least 5 years from randomization.
Secondary outcome [11] 0 0
Rate of Unsalvageable Primary Emergence
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
Rate of Percutaneous Feeding Tube Insertion and Use
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) score
Timepoint [13] 0 0
From the date of randomization, with swallowing function assessed at one year post-randomization.
Secondary outcome [14] 0 0
Functional Oral Intake Score (FOIS)
Timepoint [14] 0 0
From the date of randomization, with swallowing function assessed at one year post-randomization.
Secondary outcome [15] 0 0
Toxicity : Assessment of Treatment-Related Adverse Events Using CTCAE v5.0
Timepoint [15] 0 0
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.

Eligibility
Key inclusion criteria
Inclusion criteria for the Registration phase

* 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.

Inclusion criteria for the Randomization phase

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* Known metastatic disease
* Unable to complete QOL questionnaires
* Pregnant or lactating women

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/01/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/05/2027
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Flinders Medical Centre - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
Lawson Health Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Dr. Jake Jervis-Bardy
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Dr. David Palma
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Dr. Adam Mutsaers
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Adrian I Mendez, MD
Address 0 0
Lawson Health Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Halema Khan, PhD
Address 0 0
Country 0 0
Phone 0 0
5196858500
Fax 0 0
Email 0 0
halema.khan@lhsc.on.ca
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
The data will be available once we receive OCREB approval. Hopefully by November of 2024.
Available to whom?
Scientific researchers interested in obtaining the protocol, statistical analysis plan, informed consent form, or clinical study report for educational purposes or to participate in the trial can request these materials by contacting the principal investigator or study coordinator.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06578871