Diagnostics for the Treatment of Progressive Mucosal Lesions of the Oral Cavity: a Prospective Study

Chromosomal Instability as an Indicator for the Treatment of Progressive Mucosal Lesions of the Oral Cavity.

Despite improvements in therapy, head and neck carcinomas still have a poor prognosis with a 5-year survival of ~ 50%. Malignancies of the head and neck area are (almost) always preceded by precursor lesions. Treatment of these premalignant mucosal abnormalities is generally limited and not very inconvenient for the patient. If this precursor lesion remain untreated, it may develop into a malignancy of the head and neck. Extensive treatment will be necessary. This means loss of function of the mouth, eg chewing, speaking and swallowing.

The hypothesis is that chromosomal instability (CIN) detected by fluorescence is situ hybridization (FISH) is a reliable indicator for progression to malignancy. By intensifying the follow up and treatment in premalignant CIN lesions, the incidence of progression to invasive carcinoma is expected to be significantly reduced. If this hypothesis is justified, there will be a place for CIN detection as a risk indicator in the diagnostic work up of premalignant lesions in the head and neck.

The investigators second hypothesis is that loss of heterozygosity (LOH) detected bij DNA markers is a reliable indicator for progression to malignancy. By intensifying the outpatient clinic follow up and treatment in premalignant lesions, the incidence of progression to invasive carcinoma is expected to be significantly reduced. If this hypothesis is justified, there will be a place for CIN and LOH detection as a risk indicator in the diagnostic work up of premalignant lesions in the head and neck.

Study Overview

• Status: Withdrawn
• Conditions: Chromosomal Instability; Low Grade Dysplasia Oral Cavity; Loss of Heterozygostiy; Fluorescence In Situ Hybridization
• Intervention / Treatment: Procedure: surgery; Other: follow up

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202
      • Maastricht Universitair Medisch Centrum (MUMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• subjects ≥18 years
• premalignant lesions of the oral cavity, classified as hyperkeratosis, hyperplasia, mild or moderate dysplasia
• written informed consent

Exclusion Criteria:

• former malignancy or lesion classified as severe dysplasia or carcinoma in situ at the same anatomical localization of the oral cavity
• lesions within an anatomical field which has been exposed to former treatment (e.g. radiotherapy)
• insufficient biopsy material to perform additional FISH analysis
• pregnancy, because of the physical burden (e.g. extra general anesthesia) in this study setting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: follow up & surgery; CIN positive with surgery and intensified follow up	Procedure: surgery; excision or carbondioxide laser evaporation of the mucosal lesion of the oral cavity; Other: follow up; Intensified outpatient follow up (16 visits in 5 years)
Active Comparator: follow up; CIN positive, only intensified outpatient follow up	Other: follow up; Intensified outpatient follow up (16 visits in 5 years)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients (CIN negative and positive) who will show progression to malignancy of the oral cavity.	The primary goal of this prospective study is: Demonstrating the predictive value of the detection of CIN in premalignant lesions of the oral cavity by the use of FISH for the occurrence of progression to severe dysplasia /CIS or invasive carcinoma.; The prevention of progression of premalignant lesions of the oral cavity to severe dysplasia / CIS or invasive carcinoma by the treatment of selected high-risk lesions.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients (LOH negative and positive) who will show progression to malignancy of the oral cavity.	The secondary objective of this study is as follows: Demonstrating the predictive value of the detection of LOH in premalignant lesions of the oral cavity by the use of DNA markers for the occurrence of progression to severe dysplasia / CIS or invasive carcinoma.	1 year

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Study Director: Maarten Borgemeester, MD, University medical centre Maastricht

Study record dates

Study Major Dates

• Primary Completion (Anticipated): January 1, 2016
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chromosome Aberrations; Genomic Instability; Chromosomal Instability
• Other Study ID Numbers: NL46343.068.13