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Not yet recruiting NCT07090070

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

No phase Interventional Oral Epithelial Dysplasia (OED) Oral Squamous Cell Carcinoma (SCC)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Cohort 1 Intervention group, Cohort 2 severe/CIS margins clear, Cohort 2 p53 and severe/CIS margins clear, Cohort 3 Excision and END.
Who it may be relevant to
Registry conditions: Oral Epithelial Dysplasia (OED), Oral Squamous Cell Carcinoma (SCC). Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Evaluating Treatment Strategies for p53 Mutant Oral Epithelial Dysplasia and SCC Study

Overview

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

Interventions

  • Procedure Cohort 1 Intervention group
    Clear margin excision of the lesion under local anesthetic, with re-excision for p53-positive margins.
  • Procedure Cohort 2 severe/CIS margins clear
    Clear margin excision of the lesion under local anesthetic, with re-excision until severe/CIS margins are clear
  • Procedure Cohort 2 p53 and severe/CIS margins clear
    Excision of the lesion ensuring final negative p53 and severe/CIS margins
  • Procedure Cohort 3 Excision and END
    Excision of primary lesion and immediate elective neck dissection
  • Procedure Cohort 3 Excision and Close follow up
    Excision of primary lesion and close follow up with salvage neck dissection if development of nodal disease

Primary outcome measures

  • Progression of Disease [Time frame: 4 years]
  • Time of Disease Progression [Time frame: 4 years]
  • Recurrence of Disease [Time frame: Study 1 and 2: 4 years, Study 3: 3 years]
  • Disease-free Survival [Time frame: 3 years]
Secondary outcome measures (2)
  • Overall survival [Time frame: Study 1 and 2: 4 years, Study 3: 3 years]
  • Patient Reported Outcomes - Quality of Life and Functional Measurements [Time frame: Study 1 and 2: 4 years, Study 3: 3 years]

Eligibility criteria

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

  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Canada · 1 center
  • Vancouver General Hospital — Vancouver

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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 36906072

Identifiers

NCT: NCT07090070 · H25-01056

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗