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Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore (PREDICT-OLP)

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ClinicalTrials.gov Identifier: NCT03975322
Recruitment Status : Not yet recruiting
First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Manuel Weber, University of Erlangen-Nürnberg Medical School

Brief Summary:

Oral squamous cell carcinomas (OSCC) is among the most common malignancies worldwide. Early detection and prevention of OSCC is thought to have the highest potential to reduce morbidity and mortality. In prevention, the main focus is on precancerous lesions, especially oral leukoplakia (OLP), as up to 67% of OSCC arise on the basis of OLP. The determination of the transformation risk of OLP by histological determination of the degree of dysplasia is unreliable.

A promising marker for the timely development of a OSCC is the detection of antigens of the MAGE-A gene family. The special feature of MAGE-A is that they can be detected in 93% of all OSCC and in approx. 85% of OLP that transform to OSCC. The detection of MAGE-A could also indicate changes in the immunological environment that occur prior to malignant OLP transformation and could be used for immunotherapies.

Aim of this study is to investigate MAGE-A as a predictive marker for the malignant transformation of OLP in the setting of a prospective, multicenter study and to establish it as a diagnostic parameter in addition to classical histology. In addition, the association of MAGE-A expression with the occurrence of immunological changes in OLP will be investigated in order to evaluate the possibility of minimally invasive immunotherapy of OLP.

The study is intended to include 500 biopsies of non-selected patients with OLP from university institutions and private practices. The follow-up should be at least 3 years, whereby it is examined whether an OSCC on the basis of the original OLP developed. After three years, an interim evaluation of the results with statistical evaluation will be carried out. In order to ensure that the course of the disease is monitored for at least three years for all OLPs, an extension of the monitoring period to 5 years is planned.

The study could establish a routine diagnostic parameter to supplement the histo-morphological diagnosis of OLP and evaluate the possibility of immunotherapy of OLP.


Condition or disease
Oral Leukoplakia Oral Leukoplakia of Tongue Oral Leukoplakia of Gingiva Oral Lichen Planus

  Show Detailed Description

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 500 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 3 Years
Official Title: Prospective Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : September 30, 2024
Estimated Study Completion Date : September 30, 2026





Primary Outcome Measures :
  1. Dependence of malignant transformation on a MAGE-A based immunoscore [ Time Frame: 2 years ]

    Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated:

    • MAGE-A expression
    • Macrophage infiltration and polarization (CD68, CD163)
    • T cell infiltration (CD3, CD8)
    • Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

  2. Dependence of malignant transformation on a MAGE-A based immunoscore [ Time Frame: 3 years ]

    Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated:

    • MAGE-A expression
    • Macrophage infiltration and polarization (CD68, CD163)
    • T cell infiltration (CD3, CD8)
    • Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

  3. Dependence of malignant transformation on a MAGE-A based immunoscore [ Time Frame: 5 years ]

    Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated:

    • MAGE-A expression
    • Macrophage infiltration and polarization (CD68, CD163)
    • T cell infiltration (CD3, CD8)
    • Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore


Secondary Outcome Measures :
  1. Frequency of malignant transformation [ Time Frame: 2 years ]
    Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

  2. Frequency of malignant transformation [ Time Frame: 3 years ]
    Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

  3. Frequency of malignant transformation [ Time Frame: 5 years ]
    Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

  4. Dependence of malignant transformation on dysplasia [ Time Frame: 2 years ]
    Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)

  5. Dependence of malignant transformation on dysplasia [ Time Frame: 3 years ]
    Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)

  6. Dependence of malignant transformation on dysplasia [ Time Frame: 5 years ]
    Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)


Biospecimen Retention:   Samples Without DNA
paraffin specimens and RNAlater specimens


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with clinically proven leukoplakia (OLP) of the oral cavity (whitish, non-wipeable oral mucosa changes that cannot be attributed to any disease) are to be included in the study.
Criteria

Inclusion Criteria:

  • Adults, consenting male or female patients
  • Age 18 - 80 years
  • Diagnosis of one or more leukoplakia of the oral cavity

including

  • leukoplakia associated wit lichen planus OR
  • leukoplakia associated with diseases of the immune system or immunosuppression OR
  • leukoplakia associated with a malignoma of other sites (except oral cavity) in the anamnesis
  • Existing consent to participation in the study after clarification has been given

Exclusion Criteria:

  • clinical evidence of invasive carcinoma of the oral cavity OR
  • carcinoma of the oral cavity in the anamnesis OR
  • patients unable to give informed consent OR
  • rejection of the patient

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975322


Contacts
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Contact: Manuel Weber, MD, DMD 0049 9131 85 43749 manuel.weber@uk-erlangen.de
Contact: Falk Wehrhan, MD, DMD 0049 9131 85 43731 falk.wehrhan@uk-erlangen.de

Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
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Study Chair: Manuel Weber, MD, DMD Maxillofacial Surgery Erlangen
Study Chair: Falk Wehrhan, MD, DMD Maxillofacial Surgery Erlangen
Study Chair: Jutta Ries, PhD Maxillofacial Surgery Erlangen

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Responsible Party: Manuel Weber, Dr. med. Dr. med. dent. Manuel Weber, MD, DMD, Principal Investigator, University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT03975322     History of Changes
Other Study ID Numbers: 1.4
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Manuel Weber, University of Erlangen-Nürnberg Medical School:
OLP
oral cancer
OSCC
oral squamous cell carcinoma

Additional relevant MeSH terms:
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Lichen Planus
Lichen Planus, Oral
Leukoplakia
Leukoplakia, Oral
Lichenoid Eruptions
Skin Diseases, Papulosquamous
Skin Diseases
Mouth Diseases
Stomatognathic Diseases
Precancerous Conditions
Neoplasms
Pathological Conditions, Anatomical
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site