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

University of British Columbia

Status: Not yet enrolling

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

Treatments: Procedure: Cohort 2 p53 and severe/CIS margins clear; Procedure: Cohort 3 Excision and Close follow up; Procedure: Cohort 3 Excision and END; Procedure: Cohort 1 Intervention group; Procedure: Cohort 2 severe/CIS margins clear

Study type: Interventional

Funder types: Other

Identifiers

NCT07090070

H25-01056

Details and patient eligibility

About

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

Enrollment: 171 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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171 participants in 6 patient groups

Cohort 1: p53 mutant mild/moderate dysplasia observational group

No Intervention group

Description:

Observation only

Cohort 1: p53 mutant mild/moderate dysplasia excision group

Experimental group

Description:

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

Treatment:

Procedure: Cohort 1 Intervention group

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

Active Comparator group

Description:

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

Treatment:

Procedure: Cohort 2 severe/CIS margins clear

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

Experimental group

Description:

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

Treatment:

Procedure: Cohort 2 p53 and severe/CIS margins clear

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

Active Comparator group

Description:

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

Treatment:

Procedure: Cohort 3 Excision and END

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

Experimental group

Description:

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

Treatment:

Procedure: Cohort 3 Excision and Close follow up