Evaluating Treatment Strategies for p53 Mutant Oral Cancer and Oral Cancer Precursors: A Randomized Controlled Trial

NCT ID: NCT07090070

Last Updated: 2025-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

171 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-30

Study Completion Date

2032-09-30

Brief Summary

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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 (SCC). 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 without surgical intervention will progress to high-grade dysplasia 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\<3mm 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 END if development of nodal disease

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1: p53 mutant mild/moderate dysplasia observational group

Observation only

Group Type NO_INTERVENTION

No interventions assigned to this group

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

Group Type EXPERIMENTAL

Cohort 1 Intervention group

Intervention Type PROCEDURE

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

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

Group Type ACTIVE_COMPARATOR

Cohort 2 severe/CIS margins clear

Intervention Type 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 negative p53 and severe/CIS margin group

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

Group Type EXPERIMENTAL

Cohort 2 p53 and severe/CIS margins clear

Intervention Type PROCEDURE

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

Cohort 3: p53 mutant T1 SCC (DOI 0-3mm) excision and END group

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

Group Type ACTIVE_COMPARATOR

Cohort 3 Excision and END

Intervention Type PROCEDURE

Excision of primary lesions with 5+mm margins and immediate elective neck dissection

Cohort 3: p53 mutant T1 SCC (DOI 0-3mm) excision and follow up group

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

Group Type EXPERIMENTAL

Cohort 3 Excision and Close follow up

Intervention Type PROCEDURE

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

Interventions

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Cohort 1 Intervention group

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

Intervention Type 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

Intervention Type PROCEDURE

Cohort 2 p53 and severe/CIS margins clear

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

Intervention Type PROCEDURE

Cohort 3 Excision and END

Excision of primary lesions with 5+mm margins and immediate elective neck dissection

Intervention Type PROCEDURE

Cohort 3 Excision and Close follow up

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

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Adults age 18 or over

Cohort 1:

* Biopsy-confirmed mild/moderate dysplasia with p53 mutations (tested via IHC)
* No prior treatment for oral premalignant lesions
* No clinical evidence of SCC

Cohort 2:

* Biopsy-confirmed severe dysplasia or CIS with p53 mutation (tested via IHC)

Cohort 3:

* T1 SCC with p53 mutation (tested via IHC)
* Depth of Invasion (DOI) 0-3mm
* Clinically and radiologically node-negative (confirmed by contrast-enhanced CT)

Exclusion Criteria

* History of head and neck radiation
* Immunocompromised status
* Location of excision would be functionally morbid
* Lesions greater than 3cm
* Presence of Proliferative Verrucous Leukoplakia

Cohort 1:

* Severe dysplasia or carcinoma is situ (CIS) on initial biopsy

Cohort 2:

* Presence of invasive SCC on initial biopsy

Cohort 3:

* Positive nodes on imaging
* DOI \>= 4mm
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Eitan Prisman

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

Central Contacts

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Eitan Prisman

Role: CONTACT

6048754126

Tayo Steininger

Role: CONTACT

6048754111 ext. 22935

Facility Contacts

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Eitan Prisman

Role: primary

6048754126

References

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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.

Reference Type BACKGROUND
PMID: 26027881 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27560665 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33034628 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36522371 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39265952 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32797678 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34735529 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36906072 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39265950 (View on PubMed)

Other Identifiers

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H25-01056

Identifier Type: -

Identifier Source: org_study_id

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