Surgery and Reducing Ionizing Radiation of the Unknown Primary

NCT06578871 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 150805007
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Head and Neck Squamous Cell Carcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma

Keywords

HPV-Mediated PUK; Head and Neck Cancer; P16+; Radiation Therapy; Oropharyngeal Cancer; Squamous Cell Carcinoma; Transoral Robotic Surgery (TORS); Mucosal Radiation; SUPERIOR Trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• MD Anderson Dysphagia Inventory (MDADI)

  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: 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)

  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

  Assessed at baseline, 6 months, and 1 year post randomization

• Neck Dissection Impairment Index (NDII):

  Assessed at baseline, 6 months, and 1 year post randomization

Study Arms (2)

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

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

Procedure: Surgical Intervention; Radiation: Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck

Interventions

Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk RADIATION

Patients in Arm 1, after the surgical procedure, will receive radiotherapy to the at-risk mucosa.

Arm1: Standard of Care Treatment

Surgical Intervention PROCEDURE

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

Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck; Arm1: Standard of Care Treatment

Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck RADIATION

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

Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck; Arm1: Standard of Care Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Dr. Jake Jervis-Bardy: collaborator
• Dr. David Palma: collaborator
• Dr. Adam Mutsaers: collaborator

Study Sites (3)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, 5042, Australia

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Related Publications (21)

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MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Carcinoma, Squamous Cell

Interventions

Radiotherapy, Intensity-Modulated; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Adrian I Mendez, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

• Jake Jervis-Bardy, MD

  Royal Adelaide Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Halema Khan, PhD

CONTACT

5196858500; halema.khan@lhsc.on.ca

Adrian I Mendez, MD

CONTACT

5196858058; adrian.mendez@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The SUPERIOR trial employs a 1:2 randomization ratio using a permuted block design with block sizes known only to the statistician. Stratification factors include smoking status (\>10 pack-years vs. ≤10 pack-years) and pathologic nodal burden (1 node positive vs. \>1 node positive). Although participants and treating clinicians are aware of the treatment allocations, outcome assessors and data analysts are blinded to the treatment arms to ensure unbiased assessment and analysis of trial results.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 29, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 30, 2027
• Last Updated: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data will be available once we receive OCREB approval. Hopefully by November of 2024.
• Access Criteria: 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.

Locations

AU (2); CA (1)