Surgery and IMRT for Head and Neck Cancer

(SUPERIOR Trial)

Recruiting at 2 trial locations

Overseen By Halema Khan, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lawson Health Research Institute

Disqualifiers: EBV-positive, Metastatic disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for head and neck cancer?

Research shows that using intensity-modulated radiotherapy (IMRT) can reduce side effects while maintaining control over the tumor in head and neck cancer. Additionally, IMRT is effective in preventing the recurrence of cancer in specific lymph nodes, which supports its use in treating head and neck cancer. ^{1 2 3 4 5}

How is the treatment of Surgery and IMRT for Head and Neck Cancer unique?

This treatment combines surgery with intensity-modulated radiation therapy (IMRT), which is known for its precision in targeting cancer cells while sparing healthy tissue, potentially reducing side effects compared to traditional radiation methods. The surgical component, involving techniques like Lymphovenous Anastomosis (LVA) and Vascularized Lymph Node Transplantation (VLNT), is designed to address lymphatic issues, which is not typically a focus in standard head and neck cancer treatments. ^{1 6 7 8 9}

What is the purpose of this 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. 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.

Research Team

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

Eligibility Criteria

This trial is for people with certain head and neck cancers where the primary tumor can't be found, often linked to HPV. Participants should have cancer in their lymph nodes but no detectable primary tumor after advanced imaging and specialized surgeries.

Inclusion Criteria

For the Registration phase: Willing to provide informed consent

My neck cancer is p16 positive.

My tests show no signs of the original cancer tumor.

Exclusion Criteria

Unable to complete QOL questionnaires

I have had head or neck cancer in the past 2 years.

I have tested positive for the Epstein-Barr Virus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo neck dissection, tonsillectomy, and tongue base mucosectomy to locate and treat the primary tumour

1-2 weeks

1 visit (in-person)

Radiation

Radiotherapy is administered to the neck, with conditional omission of mucosal radiation based on trial arm

6 weeks

Daily visits (in-person) for radiation sessions

Follow-up

Participants are monitored for safety, effectiveness, and quality of life post-treatment

5 years

Regular visits at 6 months, 1 year, and annually thereafter

Treatment Details

Interventions

• Intensity Modulated Radiotherapy (IMRT) to Ipsilateral Neck
• Intensity Modulated Radiotherapy (IMRT) to Mucosa at Risk
• Surgical Intervention

Trial Overview The SUPERIOR trial is testing if less radiation or just surgery alone can treat these cancers effectively. It compares traditional treatments like full-throat radiation and node removal surgery against reduced radiation areas or possibly surgery only.

Participant Groups

Group I: Arm 2: Omission of IMRT to Risk Mucosa but conditional IMRT to Neck Experimental Treatment 2 Interventions

* If N1 with single node \<= 3cm, no further treatment * If multiple ipsilateral nodes or single ipsilateral node \>3 cm, radiation to Neck only

Group II: Arm1: Standard of Care Treatment Active Control 3 Interventions

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

Surgical Intervention is already approved in European Union, United States, Canada, Switzerland for the following indications:

Approved in European Union as Lymphovenous Anastomosis (LVA) for:

• Chronic Breast Cancer-Related Lymphedema

Approved in United States as Vascularized Lymph Node Transplantation (VLNT) for:

• Chronic Breast Cancer-Related Lymphedema

Approved in Canada as Microsurgical Intervention for:

• Chronic Breast Cancer-Related Lymphedema

Approved in Switzerland as Lymphovenous Anastomosis (LVA) for:

• Chronic Breast Cancer-Related Lymphedema

Who Is Running the Clinical Trial?

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

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

Lead Sponsor

Trials

678

Recruited

421,000+

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

Lead Sponsor

Trials

668

Recruited

424,000+

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

Lead Sponsor

Trials

686

Recruited

427,000+

Dr. David Palma

Collaborator

Trials

1

Recruited

90+

Dr. Jake Jervis-Bardy

Collaborator

Trials

1

Recruited

90+

Dr. Adam Mutsaers

Collaborator

Trials

1

Recruited

90+

Findings from Research

In a study of 200 head and neck cancer patients, reducing the radiation dose to elective nodal sites from 50Gy to 40Gy did not compromise tumor control, as there were no significant differences in survival or recurrence rates between the two groups after two years.

The lower dose (40Gy) was associated with a significant reduction in salivary gland toxicity at 6 and 18 months, suggesting a potential benefit in minimizing side effects for patients undergoing intensity-modulated radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control. Nevens, D., Duprez, F., Daisne, JF., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Volumetric change of human papillomavirus-related neck lymph nodes before, during, and shortly after intensity-modulated radiation therapy. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

Intensity-modulated Radiation Therapy for Lymph Node Oligo-recurrence. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Developing an Adaptive Radiotherapy Technique for Virally Mediated Head and Neck Cancer. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Clinical challenges in the implementation of a tomotherapy service for head and neck cancer patients in a regional UK radiotherapy centre. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy as primary treatment for oropharyngeal squamous cell carcinoma. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Transoral surgery vs intensity-modulated radiotherapy for early supraglottic cancer: a systematic review. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Carotid sparing intensity-modulated radiation therapy achieves comparable locoregional control to conventional radiotherapy in T1-2N0 laryngeal carcinoma. [2022]