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

NCT07090070 | Not Yet Recruiting

• 1 other identifier: H25-01056
• Study Type: interventional
• Target: 636
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Keywords

p53 mutant; SCC; oral epithelial dysplasia

Outcome Measures

Primary Outcomes (4)

• 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.

  4 years

• 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.

  4 years

• 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.

  Study 1 and 2: 4 years, Study 3: 3 years

• Disease-free Survival

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

  3 years

Secondary Outcomes (2)

• Overall survival

  Study 1 and 2: 4 years, Study 3: 3 years

• Patient Reported Outcomes - Quality of Life and Functional Measurements

  Study 1 and 2: 4 years, Study 3: 3 years

Study Arms (6)

Cohort 1: p53 mutant mild/moderate dysplasia observational group

NO INTERVENTION

Observation only

Cohort 1: p53 mutant mild/moderate dysplasia excision group

EXPERIMENTAL

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

Procedure: Cohort 1 Intervention group

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

ACTIVE COMPARATOR

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

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

EXPERIMENTAL

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

Procedure: Cohort 2 p53 and severe/CIS margins clear

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

ACTIVE COMPARATOR

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

Procedure: Cohort 3 Excision and END

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

EXPERIMENTAL

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

Cohort 1 Intervention group PROCEDURE

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

Cohort 1: p53 mutant mild/moderate dysplasia excision group

Cohort 2 severe/CIS margins clear PROCEDURE

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

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

Cohort 2 p53 and severe/CIS margins clear PROCEDURE

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

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

Cohort 3 Excision and END PROCEDURE

Excision of primary lesion and immediate elective neck dissection

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

Cohort 3 Excision and Close follow up PROCEDURE

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Related Publications (9)

• 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.

  PMID: 26027881 BACKGROUND

• 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.

  PMID: 27560665 BACKGROUND

• 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.

  PMID: 33034628 BACKGROUND

• 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.

  PMID: 36522371 BACKGROUND

• 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.

  PMID: 39265952 BACKGROUND

• 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.

  PMID: 32797678 BACKGROUND

• 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.

  PMID: 34735529 BACKGROUND

• 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.

  PMID: 36906072 BACKGROUND

• 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.

  PMID: 39265950 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Endoglin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Central Study Contacts

Eitan Prisman

CONTACT

6048754126; prisman.eitan@vch.ca

Tayo Steininger

CONTACT

6048754111; tayo.steininger@vch.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: July 29, 2025
• Study Start: June 1, 2026
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): September 1, 2032
• Last Updated: June 3, 2026

Record last verified: 2026-05

Locations

CA (1)