Surgery and Reducing Ionizing Radiation of the Unknown Primary
NCT Number: NCT06578871
Acronym: SUPERIOR
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma|HPV Positive Oropharyngeal Squamous Cell Carcinoma
Interventions: RADIATION: Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk|PROCEDURE: Surgical Intervention|RADIATION: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck
Sponsor: Lawson Health Research Institute
Collaborators: Dr. Jake Jervis-Bardy|Dr. David Palma|Dr. Adam Mutsaers
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 90
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2025-01-01
Completion Date: 2027-05-30
Locations: Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia|Flinders Medical Centre, Adelaide, South Australia, 5042, Australia|London Health Sciences Centre, London, Ontario, N6A 5W9, Canada

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. 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.

Primary Outcome Measures: 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., 2 years
Secondary Outcome Measures: 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., 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., 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., 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., 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., 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., 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., 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)., 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., 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., 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., 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., 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., 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., 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., 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.