Treatment Strategies for Mouth Cancer

(p53 RCT Trial)

Overseen By Tayo Steininger

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Head/neck radiation, Immunocompromised, Lesions >3cm, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by cohort

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best treatment for people with certain types of mouth cancer, specifically those with p53-mutant oral conditions. Researchers seek to determine if different surgical strategies can prevent the cancer from worsening. The study organizes participants into three groups, each testing different approaches: simple observation, various surgical techniques (such as surgical excision with clear margins or elective neck dissection), or a combination of surgery and follow-up. It suits individuals diagnosed with specific early-stage mouth conditions who have not received previous treatment for these issues. Participants will contribute to discovering better ways to manage and treat mouth cancer. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to improved treatment strategies for mouth cancer.

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 clear surgical margins are crucial for treating mouth cancer, which involves removing a small area of tissue around the cancer. Studies suggest that removing 4 to 5 millimeters or more of this tissue can improve survival rates. However, balancing this with preserving healthy tissue is important, as excessive removal can affect quality of life.

Elective neck dissection (END) involves removing lymph nodes in the neck even if cancer hasn't spread there yet. Research indicates that this procedure can help prevent cancer from spreading. Some studies have found that END may have side effects in about 6.6% of cases, which is relatively low. Overall, END appears to improve survival chances for patients with oral cancer.

Both treatments are generally well-tolerated, but like any surgery, they carry risks. Patients should discuss with their doctors to determine the best approach for their specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for mouth cancer because they explore innovative surgical strategies that differ from the standard approach. Unlike typical treatments that might involve immediate neck dissection or follow-up only if the disease progresses, these new strategies focus on clear margin excisions and precise genetic targeting. For instance, one approach ensures that severe dysplasia margins are clear before proceeding, while another targets p53-positive margins specifically. This precision could lead to more personalized and potentially less invasive treatment plans, which is a promising direction for improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for mouth cancer?

This trial will compare different surgical strategies for treating mouth cancer. Studies have shown that surgically removing mouth cancer with clear margins can help prevent recurrence. Clear margins mean all cancer cells are removed, reducing the chance of the cancer returning. Research also indicates that if cancer cells are found in the surgical margins, the risk of recurrence increases, so ensuring these margins are clear might improve outcomes.

One arm of this trial involves elective neck dissection (END), which has improved survival rates in patients with early-stage oral cancer. This procedure involves removing lymph nodes in the neck before cancer spreads to them, helping to control the disease and extend survival. Overall, studies support the effectiveness of these surgical strategies in treating mouth cancer and improving patient outcomes. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage mouth cancer or precancerous oral lesions, specifically those with p53 mutations. Participants will be grouped based on their diagnostic stage and treatment history.

Inclusion Criteria

Cohort 3: Depth of Invasion (DOI) 0-3mm

My biopsy shows mild/moderate dysplasia with p53 mutations.

My scans show no cancer in my lymph nodes.

Exclusion Criteria

Cohort 3: Positive nodes on imaging

My initial biopsy showed invasive squamous cell carcinoma.

My immune system is weakened.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are assigned to different treatment strategies based on their diagnostic cohort, including observation, surgical excision with clear margins, and elective neck dissection (END).

Varies by cohort

Follow-up

Participants are monitored for progression to severe/CIS dysplasia or SCC, disease-free survival, and overall survival.

4 years

Long-term monitoring

Continued monitoring of disease progression and survival outcomes.

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Surgical excision and close follow-up, only END if development of nodal disease
• Surgical excision and elective neck dissection (END)
• Surgical excision with clear margins
• Surgical excision with clear severe/CIS and p53 margins
• Surgical excision with clear severe/CIS margins

Trial Overview The study tests different treatments across three cohorts: Cohort 1 compares observation to surgical excision; Cohort 2 compares two types of surgical excisions; and Cohort 3 compares surgery plus elective neck dissection versus close follow-up.

How Is the Trial Designed?

Group I: Cohort 3: p53 mutant T1 SCC (DOI 0-3mm) excision and follow up group Experimental Treatment 1 Intervention

Excision of primary lesion with 5+mm margins and close follow up with salvage elective neck dissection (END) if development of nodal disease

Group II: Cohort 2: p53 mutant Severe/CIS dysplasia negative p53 and severe/CIS margin group Experimental Treatment 1 Intervention

Excision of the lesion ensuring final negative p53 and severe/CIS margins

Group III: Cohort 1: p53 mutant mild/moderate dysplasia excision group Experimental Treatment 1 Intervention

Clear margin excision of the lesion under local anesthetic, with re-excision for p53-positive margins

Group IV: Cohort 2: p53 mutant Severe/CIS dysplasia clear severe/CIS margin group Active Control 1 Intervention

Clear margin excision of the lesion under local anesthetic, with re-excision until severe/CIS margins are clear

Group V: Cohort 1: p53 mutant mild/moderate dysplasia observational group Active Control 1 Intervention

Observation only

Group VI: Cohort 3: p53 mutant T1 SCC (DOI 0-3mm) excision and END group Active Control 1 Intervention

Excision of primary lesion with 5+ mm margins and immediate elective neck dissection (END)

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Citations

1. nature.com nature.com/articles/s41598-025-96018-2

Neck dissection improves the prognosis of patients with ... Studies shown that 5-year overall survival (OS) for early-stage OSCC ranged from 60 to 70%, while 5-year disease-specific survival (DSS) ranges ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1506007

Elective versus Therapeutic Neck Dissection in Node ... Among patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than did ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2212555824001923

Is elective neck dissection effective for clinical cervical ... Considerations in favor of elective neck dissection are based on studies showing lower recurrence rates and improved survival rates, but the evidence is still ...

4. theajo.com theajo.com/article/view/4596/html

Elective neck dissection improves regional control in early ... Results: There were 95 (25.2%) instances of recurrence overall, with 35 (9.3%) regional recurrence as well as 32 deaths (8.5%) from OSCC. An ...

5. cochrane.org cochrane.org/evidence/CD006205_surgical-treatments-oral-cavity-mouth-and-oropharyngeal-throat-cancers

Surgical treatments for oral cavity (mouth) and ... The results show that elective neck dissection probably leads to longer overall and disease-free survival and less locoregional recurrence, but ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2640044/

Elective neck dissection in oral carcinoma: a critical review ... The evidence available suggests a protective effect of elective neck dissection for patients with oral cancer.

7. nature.com nature.com/articles/s41416-019-0587-2

Nationwide randomised trial evaluating elective neck ... Summary efficacy results are shown in Table 2 and Fig. 1. Among the 250 patients, there were 83 deaths (49 due to oral cancer). From the ITT ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.18.01921

Management of the Neck in Squamous Cell Carcinoma ... At 3 years, patients who received upfront END had significantly improved overall survival (80.0%; 95% CI, 74.1% to 85.8%) compared with those ...

9. journals.lww.com journals.lww.com/md-journal/fulltext/2018/12210/association_of_neck_dissection_with_survival_for.56.aspx

Association of neck dissection with survival for early... In the overall cohort, patients who underwent neck dissection had better survival than those who were managed with observation in both tongue cancer specific ...