CClinicalTrials.gg
RecruitingNCT07090070p53 RCTUpdated Sep 8, 2026

Evaluating Treatment Strategies for p53 Mutant Oral Cancer and Oral Cancer Precursors

An interventional study of Cohort 1 Intervention group and Cohort 2 severe/CIS margins clear in Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (SCC), sponsored by University of British Columbia. Recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.

Sponsored by University of British Columbia · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
636
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Oral Epithelial Dysplasia (OED)
  • Oral Squamous Cell Carcinoma (SCC)

Keywords

  • p53 mutant
  • SCC
  • oral epithelial dysplasia
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Adults age 18 or over
  • No history of head and neck radiation
  • p53-abnormal IHC patterns (surrogate marker for TP53 mutation)

Cohort 1:

  • Biopsy-confirmed mild/moderate dysplasia

Cohort 2:

  • Biopsy-confirmed severe dysplasia or CIS

Cohort 3:

  • T1 SCC with depth of Invasion (DOI) \<4mm
  • Clinically and radiologically node-negative (confirmed by contrast-enhanced CT)

Exclusion criteria

Exclusion Criteria:

  • Immunocompromised status
  • Lesions greater than 3 cm
  • Presence of Proliferative Verrucous Leukoplakia

Cohort 1:

  • Had prior treatment for oral premalignant lesions

Cohort 2:

  • Presence of invasive SCC on initial biopsy

Cohort 3:

  • Positive nodes on contrast-enhanced CT
  • DOI >= 4mm
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
636 participants (estimated)

Study arms

  • No intervention
    Cohort 1: p53 mutant mild/moderate dysplasia observational group

    Observation only

  • Experimental
    Cohort 1: p53 mutant mild/moderate dysplasia excision group

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

    Procedure: Cohort 1 Intervention group

  • Active comparator
    Cohort 2: p53 mutant Severe/CIS dysplasia clear severe/CIS margin group

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

    Procedure: Cohort 2 severe/CIS margins clear

  • Experimental
    Cohort 2: p53 mutant Severe/CIS dysplasia negative p53 and severe/CIS margin group

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

    Procedure: Cohort 2 p53 and severe/CIS margins clear

  • Active comparator
    Cohort 3: p53 mutant T1 SCC (DOI <4mm) excision and END group

    Excision of primary lesion and immediate elective neck dissection (END)

    Procedure: Cohort 3 Excision and END

  • Experimental
    Cohort 3: p53 mutant T1 SCC (DOI <4mm) excision and follow up group

    Excision of primary lesion and close follow up with salvage neck dissection if development of nodal disease

    Procedure: Cohort 3 Excision and Close follow up

Interventions

  • ProcedureCohort 1 Intervention group

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

  • ProcedureCohort 2 severe/CIS margins clear

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

  • ProcedureCohort 2 p53 and severe/CIS margins clear

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

  • ProcedureCohort 3 Excision and END

    Excision of primary lesion and immediate elective neck dissection

  • ProcedureCohort 3 Excision and Close follow up

    Excision of primary lesion and close follow up with salvage neck dissection if development of nodal disease

05

What researchers measure

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 years

  2. 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 years

  3. 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 years

  4. Disease-free Survival

    Study 3: If survival is achieved disease-free following treatment.

    Time frame: 3 years

Secondary 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 years

  2. 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 years

06

Study locations

1 of 1 sites recruiting
  • Vancouver General Hospital
    Vancouver, British Columbia, Canada
    Recruiting
07

References and documents

Publications

  • D'Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, Agarwal JP, Pantvaidya G, Chaukar D, Deshmukh A, Kane S, Arya S, Ghosh-Laskar S, Chaturvedi P, Pai P, Nair S, Nair D, Badwe R; Head and Neck Disease Management Group. Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer. N Engl J Med. 2015 Aug 6;373(6):521-9. doi: 10.1056/NEJMoa1506007. Epub 2015 May 31. PubMed 26027881 ↗
  • Liu KY, Durham JS, Wu J, Anderson DW, Prisman E, Poh CF. Nodal Disease Burden for Early-Stage Oral Cancer. JAMA Otolaryngol Head Neck Surg. 2016 Nov 1;142(11):1111-1119. doi: 10.1001/jamaoto.2016.2241. PubMed 27560665 ↗
  • Durham JS, Brasher P, Anderson DW, Yoo J, Hart R, Dort JC, Seikaly H, Kerr P, Rosin MP, Poh CF. Effect of Fluorescence Visualization-Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2020 Dec 1;146(12):1149-1155. doi: 10.1001/jamaoto.2020.3147. PubMed 33034628 ↗
  • Hyodo T, Kuribayashi N, Fukumoto C, Komiyama Y, Shiraishi R, Kamimura R, Sawatani Y, Yaguchi E, Hasegawa T, Izumi S, Wakui T, Nakashiro KI, Uchida D, Kawamata H. The mutational spectrum in whole exon of p53 in oral squamous cell carcinoma and its clinical implications. Sci Rep. 2022 Dec 15;12(1):21695. doi: 10.1038/s41598-022-25744-8. PubMed 36522371 ↗
  • Lin TY, Liu KYP, Novack R, Mattu PS, Ng TL, Hoang LN, Prisman E, Poh CF, Ko YCK. Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery. Mod Pathol. 2024 Dec;37(12):100614. doi: 10.1016/j.modpat.2024.100614. Epub 2024 Sep 10. PubMed 39265952 ↗
  • Gleber-Netto FO, Neskey D, Costa AFM, Kataria P, Rao X, Wang J, Kowalski LP, Pickering CR, Dias-Neto E, Myers JN. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma. Cancer. 2020 Oct 15;126(20):4498-4510. doi: 10.1002/cncr.33101. Epub 2020 Aug 14. PubMed 32797678 ↗
  • Liu KYP, Zhu SY, Harrison A, Chen ZY, Guillaud M, Poh CF. Quantitative nuclear phenotype signatures predict nodal disease in oral squamous cell carcinoma. PLoS One. 2021 Nov 4;16(11):e0259529. doi: 10.1371/journal.pone.0259529. eCollection 2021. PubMed 34735529 ↗
  • Novack R, Zhang L, Hoang LN, Kadhim M, Ng TL, Poh CF, Kevin Ko YC. Abnormal p53 Immunohistochemical Patterns Shed Light on the Aggressiveness of Oral Epithelial Dysplasia. Mod Pathol. 2023 Jul;36(7):100153. doi: 10.1016/j.modpat.2023.100153. Epub 2023 Mar 9. PubMed 36906072 ↗
  • Ko YCK, Liu KYP, Chen E, Zhu SY, Poh CF. p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence-A Retrospective Study in a Longitudinal Cohort. Mod Pathol. 2024 Dec;37(12):100613. doi: 10.1016/j.modpat.2024.100613. Epub 2024 Sep 10. PubMed 39265950 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT07090070
Lead sponsor
University of British Columbia
Responsible party
Eitan Prisman (Principal Investigator, University of British Columbia) — Principal investigator
First posted
Jul 29, 2025
Start date
Jul 8, 2026
Primary completion
Jan 2032 (estimated)
Completion
Sep 2032 (estimated)
Last update
Sep 8, 2026

Study contacts

Eitan Prisman
Contact
prisman.eitan@vch.ca
6048754126
Alan Wei
Contact
alan.wei@vch.ca
6048754111 ext. 22935

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion