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

Официальное название

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

Обзор

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

Вмешательства

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

Первичные конечные точки

• Progression of Disease [Срок оценки: 4 years]
• Time of Disease Progression [Срок оценки: 4 years]
• Recurrence of Disease [Срок оценки: Study 1 and 2: 4 years, Study 3: 3 years]
• Disease-free Survival [Срок оценки: 3 years]

Вторичные конечные точки (2)

• Overall survival [Срок оценки: Study 1 and 2: 4 years, Study 3: 3 years]
• Patient Reported Outcomes - Quality of Life and Functional Measurements [Срок оценки: Study 1 and 2: 4 years, Study 3: 3 years]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Vancouver General Hospital — Vancouver

Публикации

• 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

Идентификаторы

NCT: NCT07090070 · H25-01056

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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