Surgery and IMRT for Head and Neck Cancer

(SUPERIOR Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates treatments for head and neck cancer when the main tumor is undetectable, but cancer appears in the lymph nodes. It examines whether less radiation or only surgery (including Lymphovenous Anastomosis, Vascularized Lymph Node Transplantation, or other microsurgical interventions) can effectively treat HPV-linked cancers while reducing side effects like difficulty swallowing and dry mouth. The trial includes two groups: one receiving standard radiation treatment and the other with reduced or no radiation, depending on the cancer's spread. Suitable candidates have HPV-related neck cancer, have undergone surgery to remove certain tissues, and show no signs of the main tumor. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to advancements in cancer care.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that intensity-modulated radiotherapy (IMRT) is usually well-tolerated and effectively controls tumors. Studies indicate it causes fewer long-term side effects compared to older radiation methods. However, some patients may experience difficulty swallowing long after treatment.

Current data suggest that surgery can effectively treat certain types of cancer and often improves the quality of life for patients with lymphedema, a condition that can occur after cancer treatments. While this information pertains to a different condition, it provides insight into the safety of surgery.

Since this trial is in Phase 2, researchers have some evidence that these treatments are safe for humans, but they continue to gather more data to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a new approach to treating head and neck cancer by adjusting the use of Intensity-Modulated Radiation Therapy (IMRT). Unlike the standard treatment, which involves radiotherapy to both the neck and mucosal surfaces, this trial tests whether omitting IMRT to the risk mucosa—but still using it conditionally on the neck when needed—can be just as effective. This could potentially reduce side effects associated with radiation to sensitive areas, leading to a better quality of life for patients. The trial aims to find out if this tailored use of IMRT can effectively control cancer while minimizing unnecessary exposure to radiation.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that head and neck cancers caused by HPV have a high survival rate, with about 90% of patients living at least five years. This finding is encouraging for treating cancers in the lymph nodes when the main tumor is difficult to locate. New imaging techniques and specialized surgeries can now identify these tumors in 70-80% of cases. For patients with small, hidden tumors, surgery alone might suffice, but further research is needed. In this trial, one arm involves surgical intervention, while another includes Intensity-Modulated Radiotherapy (IMRT) to control tumors. IMRT has improved survival rates in many head and neck cancer cases, with studies showing positive results. Both treatments are being studied in this trial to find the best balance between effectiveness and reducing side effects. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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

My neck cancer is p16 positive.

For the Registration phase: Willing to provide informed consent

I can take care of myself but may not be able to do heavy physical work.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3479880/

Clinical evaluation of intensity-modulated radiotherapy for ... The overall survival at 5 years for Stage III and IV laryngeal cancers using the most aggressive chemoradiation approaches is only 50–60%. Escalation of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825001533

Challenges in recurrent head and neck squamous cell ... A large meta-analysis published in 2020 demonstrated that IMRT-based reirradiation can provide effective tumor control and favourable survival ...

3. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02327-z

The cost effectiveness of intensity-modulated radiation therapy ... This study concluded that in the treatment of head and neck cancer, the 3-dimensional conformal radiation therapy method appears to be cost-effective.

4. jto.org jto.org/article/S1556-0864(23)02430-9/fulltext

Comparative Effectiveness of Intensity-Modulated Proton ... Specifically, at the two-year mark, ESCC-specific survival rates for patients undergoing IMPT and IMRT stood at 62.03% and 51.77%, respectively.

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2805682

Weekly Adaptive Radiotherapy vs Standard Intensity ... However, to our knowledge, no phase 3 trial has distinctly demonstrated the benefit of ART in head and neck cancer or in any tumor localization.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16763274/

Intensity-modulated radiotherapy in the standard ... Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655512001355

Intensity-modulated Radiotherapy in the Treatment of Head ... This systematic review examined the evidence for IMRT compared with two-dimensional external beam radiotherapy (EBRT) in the treatment of head and neck cancer.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e21056

Preliminary safety results of a phase II study investigating ... Assuming a CI of 20%, the risk is 0.3%. None of the 11 pts who have completed protocol therapy have experienced a recurrence. Conclusions: The ...

9. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/imrt-matches-proton-therapy-in-patient-reported-outcomes-for

Intensity-modulated radiation therapy (IMRT) matches ... Both advanced radiation approaches resulted in excellent tumor control and notably fewer long-term side effects than expected. Initial results ...

10. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00265-6/fulltext

Dysphagia-optimised intensity-modulated radiotherapy ... The literature showed that poor swallowing outcomes affect most patients with head and neck cancer in the long-term after radiotherapy.