Innovative Approach to Triage Oral Precancer

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Brief Title

Innovative Approach to Triage Oral Precancer

Official Title

Biomarker-driven Approach to Develop Population-wide Cost-effective Prevention Strategies for High-risk Oral Premalignancies

Brief Summary

      Oral cancer is a major health problem worldwide, accounting for 274,000 new cases and 145,000
      deaths annually. On average, half of the patients die within 5 years of an oral cancer
      diagnosis. Most troubling, however, is the lack of significant change in prognosis for this
      disease over the last 4 decades, even in developed nations. Even when successful, treatment
      of oral cancer can be devastating due to diminished quality of life and disfigurement. The
      key to controlling this disease is early identification of lesions that are at high risk of
      progression and provide effective treatment. The overall objective of the team is to
      integrate clinical, pathological, molecular, and imaging data to create a robust oral cancer
      risk model to predict the risk of progression of OPLs and to develop population-wide
      cost-effective prevention strategies for high-risk oral premalignancies. The project will
      involve 4 specific aims as described in detail below.

      Aim 1. To use molecular data to stratify low-grade OPLs into high- and low-risk groups.

      Aim 2. To evaluate the cost-effectiveness of various follow-up frequency that use LOH at
      chromosome 9p21 as a risk marker.

      Aim 3: To evaluate the specificity and sensitivity of using imaging technologies as a tool
      for the decision of the high-grade or high-risk biopsy site.

      Aim 4. To assess the clinical utility of a miRNA expression signature derived from serum
      collected from patients with oral cancer and OPLs.
    

Detailed Description

      1. Patient accrual This study will be occurring at the Otolaryngology Clinic, Vancouver
           General Hospital. Three hundred and sixty volunteer subjects will be enrolled to
           participate in the study. Detailed steps of the study patient accrual are provided
           below.

             1. The establishment of referral pipelines for a true population-based OPL cohort in
                BC.

                In BC, the BC Oral Biopsy Service (OBS) and the Pathology Department at Vancouver
                General Hospital (VGH) receive biopsy and surgical specimens from the dental and
                medical communities, respectively. These centralized biopsy services offer a very
                rare opportunity to establish a population-based cohort of OPLs. The pathologists
                team will identify eligible patients through the pathology sign-out process and
                call the submitting physicians to notify the potential referral pipeline as an
                alternative management for these patients. Currently, a referral pipeline for
                severe dysplasia or more advanced oral malignancy using this model exists and has
                been established to refer surgical patients for the TFRI-funded COOLS trial (by
                Drs. Durham and Poh; H09-03090). This same system/pipeline will be used to identify
                eligible patients diagnosed with mild and/or moderate dysplasias identified from
                both medical and dental communities.

             2. Eligibility Subjects over the age of 19 attend the Dental or Otolaryngology clinic
                at the Vancouver General Hospital (Vancouver Acute) for assessment of oral lesions
                diagnosed with mild or moderate dysplasia; are willing to give the informed
                consent.

             3. Recruitment & informed consent procedures A letter of invitation regarding this
                study will be mailed to the potentially eligible patients a week before their
                appointment date along with the consent document. On the day of the clinical visit,
                the research assistant will explain the study to the eligible subject and acquire
                signed consent from the participants. 400 subjects will be recruited. These
                patients will be monitored once every six months (the current standard of care).
                When clinically warranted due to signs of disease progression or at the 2-year
                follow-up mark, two 5-mm punch biopsies will be performed on lesion areas with
                different severity (as determined by imaging technologies). Two-year comparative
                biopsy at a stable lesion is current standard of care.

        2. Study procedures The study is a longitudinal study following the follow-up schedule of
           the current standard of care for such lesions, i.e., once per 6 months and comparative
           biopsy once per 2-3 years. The important time points are initial visit (baseline), at
           the end of second, 5th and 8th year of follow up visits. However, the time of biopsy is
           solely based on the clinical judgment of the clinicians, i.e., signs of disease
           progression.

             1. Clinical data collection After the subject has consented, they will be asked to
                complete a set of questionnaires for the collection of demographics and risk factor
                information. The subject will be assigned a study ID and no unique identifier will
                be linked to the data collected. A separate file will be used to link the study ID
                and patient identifiers. This is important to facilitate patient management and
                capture the outcome information. This file with patients' unique identifier will be
                kept in the pass-word protected file in the BC Cancer Research Centre (BCCRC)
                computer in a locked office in the BCCCRC and only PIs can access the file. The
                health status and HAI questionnaire is not for diagnostic purposes. Should the
                clinicians believe there is depression or anxiety present in the participant
                (clinicians' clinical judgment), the study clinicians in charge of this specific
                participant will communicate with patient's family doctor and refer the participant
                to a proper source for further evaluation and management.

             2. Data collection using study device

                  -  The clinicians will examine the patients using WL, VELScope VX for FV
                     (previously approved, R05-0116), OCT (previously approved, H09-01955), and a
                     hand-held confocal microscope (H11-00011).

                  -  OCT imaging: After identifying the abnormal areas for biopsy using WL and FV
                     examination, the clinician will place a fiber-optic probe of the OCT on the
                     oral mucosal areas of interest. The site for placement of the probe will be
                     determined by PIs (Otolaryngology-head and neck surgeons (SD/DA) and/or Oral
                     Medicine/Oral Pathology Specialist (Ng/Poh)). The images will be recorded by
                     the machine for later analysis.

                  -  Confocal microscope imaging: After OCT imaging, the clinician will apply 0.05%
                     Acriflavine Hydrochloride solution topically on the oral mucosal areas of
                     interest for 30 seconds prior to imaging. The clinician will place a hand-held
                     confocal microscope on the mucosal surface to record the observation for later
                     analysis.

                  -  All necessary efforts will be taken to reduce any mild discomfort that could
                     be associated with the probe placement inside the oral cavity of a subject.
                     The OCT probe or the confocal microscope will be covered by a plastic barrier
                     and disinfected by standard methods used for oral cavity instruments before
                     and after subject usage. The device examination will take no more than 15
                     minutes in addition to the subject's appointment time for their routine
                     visits. The maximum intensity of tissue illumination for each measurement will
                     be less than the Threshold Limit Value (TLV) established by the American
                     Conference of Governmental Industrial Hygienists (ACGIH)11 for exposure to
                     broadband light.

                  -  The information obtained from polarized reflectance measurements will be
                     compared with the histology and quantitative pathology (nuclear phenotype
                     score) of the tissue sections from the lesion. The collected spectra data from
                     normal looking areas from adjacent normal looking mucosa and contralateral
                     mucosa will be used to determine patient to patient variation in the polarized
                     reflectance of oral mucosa.

             3. Exfoliative brushing sample collection (previously approved, R05-0116) An Innovatec
                cytology brush (Arcona Inc) is used to collect exfoliated cells from the oral
                lesion. These brushings are transferred into PreservCyt® Solution (Cytyc Corp.) and
                keep in 4ºC fridge.

             4. Blood sample collection In total, 12 ml (3/4 of a tablespoon) of blood sample will
                be collected in 1 SST and 1 EDTA vacutainers in the clinic by trained research
                personnel. The blood sample will be processed and serum, plasma and puffy coat
                samples will be aliquot and frozen in -80ºC for future analysis. The DNA samples in
                the puffy coat will be extracted and used as the normal control sample for the loss
                of heterozygosity (LOH) analysis. A separate consent will be used for this purpose.
                We anticipate that all aliquots of serum, plasma and puffy coat will be used up.
                Any remaining tissue will not be discarded or sold, but will be stored in a locked
                freezer room at the BC Cancer Agency for a period of up to fifteen years so that
                results of this study can be confirmed.

             5. Frozen tissue collection In the event of biopsy, tissue will be bisected. Half of
                the sample will be fixed in the formalin solution and sent to the pathology
                laboratory for analysis as a normal part of medical diagnosis procedure. Part of
                this tissue will be kept and used only after the diagnosis has been made. At no
                time will tissue be removed solely for the purpose of research. The donated tissue
                will be given a code for identification by the project leader, and will be kept in
                secure freezers at the BC Cancer Agency until genetic material (DNA and RNA) has
                been extracted for analysis. A separate consent will be used for this purpose. We
                anticipate that all donated tissue will be used up. Any remaining tissue will not
                be discarded or sold, but will be stored in a locked freezer room at the BC Cancer
                Agency for a period of up to fifteen years so that results of this study can be
                confirmed.

             6. Tissue microdissection and DNA extraction. The formalin-fixed, paraffin-embedded
                tissue blocks of the initial biopsy and biopsy from the follow-up visit will be
                obtained from the Department of Anatomical Pathology, the Vancouver General
                Hospital. at the time of clinical change or at 24 months follow-up visit will be
                requested for processing. Ten 10-µm thick sections for DNA sample, 2 4-µm unstained
                tissue sections for quantitative histological analysis. Areas of dysplasia on the
                thick sections will be identified and microdissected. The DNA sample from the
                epithelium will be extracted and used for the LOH analysis.
    


Study Type

Observational [Patient Registry]


Primary Outcome

Cancer progression


Condition

Oral Cancer



Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

360

Start Date

November 15, 2011

Completion Date

November 14, 2022

Primary Completion Date

November 14, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Is age 19 or older

          -  Have an abnormal lesion in the mouth.

          -  able to give informed consent to participate

        Exclusion Criteria:

          -  less than 19 years old
      

Gender

All

Ages

19 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Catherine Poh, 6046758000, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT03202810

Organization ID

H11-02516


Responsible Party

Sponsor

Study Sponsor

British Columbia Cancer Agency

Collaborators

 BC Cancer Foundation

Study Sponsor

Catherine Poh, Principal Investigator, British Columbia Cancer Agency


Verification Date

June 2017