Oral Epithelial Dysplasia, Mild or Moderate GradeNCT00835341

Methylation of p16 CpG Island And Malignant Transformation of Oral Epithelial Dysplasia

An observational study of Oral Epithelial Dysplasia, Mild or Moderate Grade, run by Peking University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Oral epithelial dysplasia (OED) is one of the common precancerous lesions among Chinese adults. Biomarker is not available for detection of malignant potential of OED till now. p16 is an important tumor suppressor gene, which is inactivated frequently by methylation of CpG island in early stage of carcinogenesis. Read more about this study

Who is it for?: Any age
Conditions the study is for: Oral Epithelial Dysplasia, Mild or Moderate Grade
Type of treatment: Pill or oral medicine
How many people: 93 participants
Where: 1 siteChina
Study dates: Mar 2005to Oct 2008
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Study population: 101 patients with mild or moderate OED were selected from cases with oral leukoplakia, lichen planus, or chronic discoid erythematosus at Peking University School of Stomatology between 1995 and 2005. All of the patients with OED had been diagnosed pathologically by at least two senior pathologists using the criteria from '2005 WHO Classification System' (Gale et al, 2005). All cases involved primary lesions without any LASER, radiation therapy or chemotherapy. p16 methylation status of OED samples was analyzed with methylation-specific PCR combined with denatured high performance liquid chromatography (Sun et al, 2004). 93 eligible cases with p16-methylated or p16-unmethylated OED were enrolled into the cohort study.

Who may be able to join

histological diagnosis of mild or moderate grade OED; and
enough amount of tissue sample from OED lesion for genomic DNA extraction; and
available of methylation status of p16 CpG island in the extracted DNA sample.

Who cannot join

histological diagnosis of severe grade OED or malignant disease; or
amount of tissue sample is not enough for preparation of genomic DNA (20ng); or
quality of the prepared DNA is not good enough for detection of p16 methylation; or
OED treatment history by LASER, radiotherapy, or chemotherapy

Trial locations and contacts

1 site in 1 country.

China1 site

Department of Oral Medicine, Peking University School and Hospital of Stomatology
Beijing, 100081

Other trials in China

About this study

Official title: A Cohort Study on Prediction of Malignant Transformation of Oral Epithelial Dysplasia by p16 Methylation

Read the detailed description

Background: Identification of malignant potential of oral epithelial dysplasia (OED) is virtually impossible on histopathological grounds alone. Inactivation of p16 gene by CpG methylation is an early frequent event during oral carcinogenesis. To investigate the predictive value of p16 methylation on malignant potential in OED, we carried out the prospective cohort study.
Methods: 101 patients with histologically confirmed mild or moderate OED were included in the present study. Baseline information of p16 methylation status of the OED lesions from 93 cases was obtained by methylation-specific PCR. Progression of the OEDs lesions was examined in 78 cases histologically during the 45.8 months double-blind followup survey (78/93). The association between p16 methylation and progression of OED was analyzed with SPSS13.0 software. All P-values were two-sided.

Conditions: Oral Epithelial Dysplasia, Mild or Moderate Grade
Keywords: oral epithelial dysplasia, p16 methylation, prognosis, malignant transformation, oral squamous cell carcinoma
Medical subject headings: Lymphoma, Follicular, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00835341
Study group	Role	What they receive
p16-methylated		patients with mild or moderate oral epithelial dysplasia containing methylated p16 CpG island.
p16-unmethylated		patients with mild or moderate oral epithelial dysplasia NOT containing methylated p16 CpG island.

What is being measured

The primary outcome is the main question the study is designed to answer.

The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia
The follow-up examination was carried out with a 3-month interval. Re-biopsy was done as clinically indicated, e.g. the lesion recurs or has tendency for malignant development. Pathologic diagnosis was made by at least two pathologists without the knowledge of baseline p16 methylation, based on the World Health Organization's criteria, at Peking University School of Stomatology. The number of participants with malignant transformation of oral dysplasia was calculated based on the number of participants with oral dysplasia progressed to carcinoma by the end of the trial in each cohorts.
Measured: from 3 months to 124 months

Secondary outcomes (1)

Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia
Measured: from 3 months to 124 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2005Oct 2008

First posted3 Feb 2009 (estimated)
Study startMar 2005
Primary completionOct 2008
Study completionOct 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Oral Epithelial Dysplasia, Mild or Moderate GradeStudies of the same condition, open and under way.
More trials run by Peking UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 93 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00835341
Sponsor's protocol ID: CPDHS-434
Status last verified: May 2015
First submitted: 2 Feb 2009
Last updated: 1 Jun 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Gale N, Westra W, Pilch BZ, et al. Epithelial precursors lesions. In: Barnes L, Eveson JW, Reichart P, et al. eds. World Health Organization Classification of Tumors: Pathology and Genetics of Head and Neck Tumors. IARC Press, Lyon (France); 2005: 177-179.
Sun Y, Deng D, You WC, Bai H, Zhang L, Zhou J, Shen L, Ma JL, Xie YQ, Li JY. Methylation of p16 CpG islands associated with malignant transformation of gastric dysplasia in a population-based study. Clin Cancer Res. 2004 Aug 1;10(15):5087-93. doi: 10.1158/1078-0432.CCR-03-0622.
PubMed 15297411
Cao J, Zhou J, Gao Y, Gu L, Meng H, Liu H, Deng D. Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study. Clin Cancer Res. 2009 Aug 15;15(16):5178-83. doi: 10.1158/1078-0432.CCR-09-0580. Epub 2009 Aug 11.
PubMed 19671846

Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Cohort Study on Prediction of Malignant Transformation of Oral Epithelial Dysplasia by p16 Methylation
ClinicalTrials.gov ID: NCT00835341
Acronym / sponsor ID: CPDHS-434
Conditions: Oral Epithelial Dysplasia, Mild or Moderate Grade
Keywords: oral epithelial dysplasia, p16 methylation, prognosis, malignant transformation, oral squamous cell carcinoma
Study type: Observational
Recruitment status: Completed
Enrolment: 93 participants (actual)
Lead sponsor: Peking UniversityUniversity, hospital or other
Study start: Mar 2005
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 3 Feb 2009 (estimated)
Results: Posted 23 Feb 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Background: Identification of malignant potential of oral epithelial dysplasia (OED) is virtually impossible on histopathological grounds alone. Inactivation of p16 gene by CpG methylation is an early frequent event during oral carcinogenesis. To investigate the predictive value of p16 methylation on malignant potential in OED, we carried out the prospective cohort study.
Methods: 101 patients with histologically confirmed mild or moderate OED were included in the present study. Baseline information of p16 methylation status of the OED lesions from 93 cases was obtained by methylation-specific PCR. Progression of the OEDs lesions was examined in 78 cases histologically during the 45.8 months double-blind followup survey (78/93). The association between p16 methylation and progression of OED was analyzed with SPSS13.0 software. All P-values were two-sided.

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
p16-methylated	–	–patients with mild or moderate oral epithelial dysplasia containing methylated p16 CpG island.
p16-unmethylated	–	–patients with mild or moderate oral epithelial dysplasia NOT containing methylated p16 CpG island.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: 101 patients with mild or moderate OED were selected from cases with oral leukoplakia, lichen planus, or chronic discoid erythematosus at Peking University School of Stomatology between 1995 and 2005. All of the patients with OED had been diagnosed pathologically by at least two senior pathologists using the criteria from '2005 WHO Classification System' (Gale et al, 2005). All cases involved primary lesions without any LASER, radiation therapy or chemotherapy. p16 methylation status of OED samples was analyzed with methylation-specific PCR combined with denatured high performance liquid chromatography (Sun et al, 2004). 93 eligible cases with p16-methylated or p16-unmethylated OED were enrolled into the cohort study.

Key inclusion criteria (3 listed)

histological diagnosis of mild or moderate grade OED; and
enough amount of tissue sample from OED lesion for genomic DNA extraction; and
available of methylation status of p16 CpG island in the extracted DNA sample.

Key exclusion criteria (4 listed)

histological diagnosis of severe grade OED or malignant disease; or
amount of tissue sample is not enough for preparation of genomic DNA (20ng); or
quality of the prepared DNA is not good enough for detection of p16 methylation; or
OED treatment history by LASER, radiotherapy, or chemotherapy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia
Time frame: from 3 months to 124 months
The follow-up examination was carried out with a 3-month interval. Re-biopsy was done as clinically indicated, e.g. the lesion recurs or has tendency for malignant development. Pathologic diagnosis was made by at least two pathologists without the knowledge of baseline p16 methylation, based on the World Health Organization's criteria, at Peking University School of Stomatology. The number of participants with malignant transformation of oral dysplasia was calculated based on the number of participants with oral dysplasia progressed to carcinoma by the end of the trial in each cohorts.

1 secondary outcome

Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia
Time frame: from 3 months to 124 months

Results and safety

Results posted to the registry on 23 Feb 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
p16-methylated	35	32
p16-unmethylated	58	46

Primary outcome: The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia

Time frame: from 3 months to 124 months. Number. Unit: participants

Measure	p16-methylated n = 35	p16-unmethylated n = 58
Value	32	46

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
p16-methylated	0 of 35 (0%)	0 of 35 (0%)	Not reported
p16-unmethylated	0 of 58 (0%)	0 of 58 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundGale N, Westra W, Pilch BZ, et al. Epithelial precursors lesions. In: Barnes L, Eveson JW, Reichart P, et al. eds. World Health Organization Classification of Tumors: Pathology and Genetics of Head and Neck Tumors. IARC Press, Lyon (France); 2005: 177-179.
Background: PubMed 15297411Sun Y, Deng D, You WC, Bai H, Zhang L, Zhou J, Shen L, Ma JL, Xie YQ, Li JY. Methylation of p16 CpG islands associated with malignant transformation of gastric dysplasia in a population-based study. Clin Cancer Res. 2004 Aug 1;10(15):5087-93. doi: 10.1158/1078-0432.CCR-03-0622.
Results publication: PubMed 19671846Cao J, Zhou J, Gao Y, Gu L, Meng H, Liu H, Deng D. Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study. Clin Cancer Res. 2009 Aug 15;15(16):5178-83. doi: 10.1158/1078-0432.CCR-09-0580. Epub 2009 Aug 11.
Beijing Cancer Hospital/ Institute, Peking University School of OncologyLink provided by the sponsor.
Peking University School of StomatologyLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dajun Deng, MD study director

Beijing Cancer Hospital/ Institue, Peking University School of Oncology

Hongwei Liu, MD, PhD principal investigator

Peking University School of Stomatology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Oral Epithelial Dysplasia, Mild or Moderate Grade, run by Peking University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia (time frame: from 3 months to 124 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00835341, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2015.