Evaluating Treatment Strategies for p53 Mutant Oral Cancer and Oral Cancer Precursors
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of British Columbia
About this trial
The goal of this clinical trial is to optimize treatment strategies for patients with p53-mutant oral epithelial dysplasia (OED) and early-stage oral squamous cell carcinoma (OSCC). The main question it aims to answer is what the most optimal treatment is at each diagnostic stage. It is hypothesized that lesions with p53-abnormal low-grade dysplasia (LGD) without surgical intervention will progress to high-grade dysplasia (HGD) or SCC in 4 years. It is also predicted that a clear p53 and severe/CIS excision margins in patients with p53-abnormal HGD will reduce the progression to invasive SCC, compared to clear severe/CIS margins, within 4 years. Finally, it is thought that patients with p53-abnormal cT1N0 and DOI\<4mm receiving an END will have improved disease free and overall survival. This research will elucidate whether or not these hypotheses are correct.
Participants in each diagnostic cohort will be assigned to one of two different treatment options, listed below:
Cohort 1:
A) No intervention, observation only B) Surgical excision with clear margins
Cohort 2:
A) Surgical excision with clear severe/CIS margins B) Surgical excision with clear severe/CIS and p53 margins
Cohort 3:
A) Surgical excision and elective neck dissection (END) B) Surgical excision and close follow-up, only salvage ND if development of nodal disease
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adults age 18 or over
No history of head and neck radiation
p53-abnormal IHC patterns (surrogate marker for TP53 mutation)
Biopsy-confirmed mild/moderate dysplasia
Disqualifiers
Immunocompromised status
Lesions greater than 3 cm
Presence of Proliferative Verrucous Leukoplakia
Had prior treatment for oral premalignant lesions
Trial design
Design model
Parallel
Treatments tested in this trial
Cohort 1 Intervention group
Procedure/SurgeryClear margin excision of the lesion under local anesthetic, with re-excision for p53-positive margins.
Cohort 2 severe/CIS margins clear
Procedure/SurgeryClear margin excision of the lesion under local anesthetic, with re-excision until severe/CIS margins are clear
Cohort 2 p53 and severe/CIS margins clear
Procedure/SurgeryExcision of the lesion ensuring final negative p53 and severe/CIS margins
Cohort 3 Excision and END
Procedure/SurgeryExcision of primary lesion and immediate elective neck dissection
Cohort 3 Excision and Close follow up
Procedure/SurgeryExcision of primary lesion and close follow up with salvage neck dissection if development of nodal disease
Treatment groups
636 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Cohort 1: p53 mutant mild/moderate dysplasia observational groupNo intervention 0 interventions
Group B: Cohort 1: p53 mutant mild/moderate dysplasia excision groupExperimental treatment 1 intervention
Group C: Cohort 2: p53 mutant Severe/CIS dysplasia clear severe/CIS margin groupActive comparator 1 intervention
Group D: Cohort 2: p53 mutant Severe/CIS dysplasia negative p53 and severe/CIS margin groupExperimental treatment 1 intervention
Group E: Cohort 3: p53 mutant T1 SCC (DOI <4mm) excision and END groupActive comparator 1 intervention
Group F: Cohort 3: p53 mutant T1 SCC (DOI <4mm) excision and follow up groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Progression of Disease
Study 1: Whether diagnosis progressed from low-grade dysplasia (mild/moderate OED) to high-grade (severe/CIS) dysplasia or OSCC. Study 2: Whether diagnosis progressed from high-grade (severe/CIS) dysplasia to OSCC.
Time frame
4 years2
Time of Disease Progression
Study 1: Time for disease to progress from low-grade dysplasia (mild/moderate OED) to high-grade (severe/CIS) dysplasia or OSCC. Study 2: Time for disease to progress from high-grade (severe/CIS) dysplasia to OSCC.
Time frame
4 years3
Recurrence of Disease
Study 1: Whether recurrence of low-grade dysplasia is present. Study 2: Whether recurrence of high-grade dysplasia is present. Study 3: Whether recurrence of OSCC is present, and if recurrence pattern is local recurrence or nodal metastasis. All: Time for disease to recur.
Time frame
Study 1 and 2: 4 years, Study 3: 3 years4
Disease-free Survival
Study 3: If survival is achieved disease-free following treatment.
Time frame
3 yearsSecondary outcomes
1
Overall survival
Overall survival is measured as survival for 4 years following diagnosis and treatment. Cause of death will be included, if applicable.
Time frame
Study 1 and 2: 4 years, Study 3: 3 years2
Patient Reported Outcomes - Quality of Life and Functional Measurements
Patient quality of life: 1. Oral Health Impact Profile-14 (OHIP) - 14 questions on a 5 point Likert scale (0-4), total ranging from 0-56, with higher scores indicating worse quality of life. 2. Hospital Anxiety and Depression Scale (HADS) - 14 questions on a 4 point Likert scale (0-3), total ranging from 0-21, with higher scores indicating increased severity or probability of depression and anxiety. Functional measurement: 1\. MD Anderson Dysphagia Inventory (MDADI) - 20 questions on a 5 point Likert scale (1-5), score total ranging from 20-100, with lower scores indicating more severe limitations.
Time frame
Study 1 and 2: 4 years, Study 3: 3 yearsSponsors and contacts
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Source ClinicalTrials.gov