Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions

Learn more about:
Related Clinical Trial
Oral Microbioma and Oral Malignant Disease Tolerance and Benefits of Mandibular Advanced Device for Snoring and Sleep Apnea in Oropharyngeal Cancer. Radial Forearm Donor Site Closure Oral Cancer Awareness in Egypt Predictive Value of GOCCLES® Device for Early Diagnosis of Oral Potentially Malignant Disorders Therapeutic Efficacy of Quercetin Versus Its Encapsulated Nanoparticle on Tongue Squamous Cell Carcinoma Cell Line Mandibular Reconstruction Preplanning (ViPMR) the Oncogenic Potential of Salivary miRNA-93 and miRNA-412-3P in Oral Lichen Planus Patients Newer Therapeutic Targets in Head and Neck Cancers Lateral Arm Free Flap for Reconstruction of the Oral Cavity and Head and Neck Soft Tissue Defects. Improved Implant for Reconstruction Purposes After Mandibular Resection Cell-free Tumor DNA in Head and Neck Cancer Patients Exploring the Application Value of PET Molecular Imaging Targeting FAP in Oral Squamous Cell Carcinoma Exfoliated Cytology in Detection of Oral Premalignant and Malignant Lesions The Oral Microbiome in OSCC The Link Between Periodontitis, Smoking and Oral Cancer Research on Optimization and Evaluation of Oral Cancer Screening Methods Low-Cost, Portable Flexible Nasopharyngoscope in Head & Neck Cancers in Low Resource Settings Topical Aldara (Imiquimod) for Oral Cancer Diagnostic Accuracy of Salivary Gamma-synuclein in Oral Malignant and Premalignant Lesions LLL Phototherapy in Oral Lesions Resulting From Anti-neoplastic Treatment Enhancing Self Care Among Oral Cancer Survivors: The Empowered Survival Trial Understanding Non-radiotherapy-based Development of Trismus Use of Ultrasound for Measuring Size of Oral Tongue Cancers Green Tea Mouthwash on the Oral Health Status in Oral Cancer Patients Oral Cancer Screening and Education in Hong Kong Evaluating Oral Visual Inspection in the Control of Oral Cancer Inductive Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients Effects of EMG Visual Feedback for Spinal Accessory Nerve Dysfunction After Neck Dissection: a Randomized Clinical Trial Prevention of Oral DNA Damage by Black Raspberries Inductive Camrelizumab and Apatinib for Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma NBI in Oral Cavity Cancer Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer 18F-FPPRGD2 PET/CT or PET/MRI in Predicting Early Response in Patients With Cancer Receiving Anti-Angiogenesis Therapy Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene Photodynamic Therapy System for Patients With Refractory/Unresponsive Solid Tumors Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma A Longitudinal Study of Plasma EBV DNA in Nasopharyngeal Carcinoma From Both Endemic and Non-Endemic Patient Populations Radiation Therapy and Bortezomib and Cetuximab With or Without Cisplatin to Treat Head and Neck Cancer Physical Activities by Technology Help (PATH) Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC Very Intense Radiotherapy-Chemotherapy Regimen in Advanced HNSCC Role of Neo-adjuvant Chemotherapy in Tongue Preservation in Locally Advanced Squamous Cell Carcinoma of Oral Tongue Study of Pre-operative Combination Therapy With Mogamulizumab and Nivolumab Against Solid Cancer Patients Patient Evaluation for Head and Neck Surgery Branch Studies Complete Decongestive Therapy (CDT) for Treatment of Head and Neck Lymphedema Neoadjuvant Erbitux Based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer Quality of Life in Patients Treated for Tongue and/or Jaw Neoplasia Before and After Speech Therapy Prospective Analysis of Robot-Assisted Surgery Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery Extended Follow-Up of Young Women in Costa Rica Who Received Vaccination Against Human Papillomavirus Types 16 and 18 and Unvaccinated Controls Clinical Evaluation of the OncAlert RAPID in Subjects Presenting for Evaluation and/or Initial Biopsy; Impact on Decision-Making Neo-adjuvant Erbitux-based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer Cigarette Smoking and Oral Microbiota Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma Therapeutic Effect Of Luteolin Natural Extract Versus Its Nanoparticles On Tongue Squamous Cell Carcinoma Cell Line The Role of Lymphangiogenesis in Head and Neck Cancer Metastasis Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis. MSOT Using Cetuximab-800CW for Detection of Cervical Lymph Node Metastases Oral Care Protocol for the Management of Chemotherapy and Radiation Therapy-Induced Oral Mucositis Least Invasive Nonlinear Light Microscopy Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN Trismus Trial of Therabite vs Wooden Spatula in Head and Neck Cancer Patients Improving Access to Control of Diseases for Women IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC Submandibular Gland Preservation in Neck Dissection uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer Postoperative Radiotherapy According to Molecular Analysis of Surgical Margins of Oral and Oropharyngeal SCC Autofluorescence Detection of Oral Malignancies and Database and Biospecimen Collection to Identify Biomarkers of Head and Neck Tumor Progression The Use of Functional Confections in Promoting Oral Health The Oral Microbiome and Upper Aerodigestive Squamous Cell Cancer A Study of Neoadjuvant Bio-C/T Followed by Concurrent Bio-R/T in High-risk Locally Advanced Oral Squamous Cell Carcinoma The Study of p62/SQSTM1 as a Malignant Transformation Marker for Oral Potentially Malignant Disorders and a Prognostic Marker for Oral Squamous Cell Carcinoma Evaluation of the Photobiomodulation Using LED Lamp for Curative Treatment of Radio-induced Mucositis. Spectroscopy for Diagnostic Assessment of Oral Mucosal Lesions Wild Type p53 Adenovirus for Oral Premalignancies Acupuncture Effect on Digestion in Critically Ill Post-Operative Oral and Hypo-pharyngeal Cancer Patients Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions Trial of IIb Preserving Neck Dissection Expression of Hypoxia-Inducible Factor-α in Oral Precancers and Cancers Diagnosis of Oral Precancers and Cancers Using Optic Coherence Tomography Innovative Approach to Triage Oral Precancer The Role of SDF-1/CXCR4 in Metastasis of Oral Squamous Cell Carcinoma Rehabilitation Outcomes in Head and Neck Survivors Evaluation of a Multispectral Vision Enhancement System for Assessment of Oral Mucosal Lesions The Relation of Microtubule-Associated Protein 2 and Cell Migration Sensitivity and Specificity of Serum and Salivary CYFRA21-1 in the Detection of Malignant Transformation in Oral Potentially Malignant Mucosal Lesions (Diagnostic Accuracy Study) Prosthesis Guided Speech Rehabilitation of T1/T2 Cancers of the Tongue Oral Pathology Asynchronous Telementoring Pilot Study Polarized Reflectance Spectroscopy for Oral Lesions A Study of the Effects of PEITC on Oral Cells With Mutant p53 Diagnostic Accuracy of Salivary DNA Integrity Index in Oral Malignant and Premalignant Lesions Analysis of the Variation in Caspase-8 Availability and Cleavage in Oral Squamous Cell Carcinoma The Role of microRNA-29b in the Oral Squamous Cell Carcinoma Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer – COOLS TRIAL Assessment of Mandibular Bone Invasion With MRI Using SWIFT Effect of FDG-PET/CT for Simulation and Radiation Treatment Planning in Oral Cancer Patients Epstein-Barr Detection in Oral Cancer Workplace Tobacco Cessation And Oral Cancer Screening Study Low-cost Enabling Technology for Image-guided Photodynamic Therapy (PDT) of Oral Cancer Cancer. Elective vs Therapeutic Neck Dissection in Treatment of Early Node Negative Squamous Carcinoma of Oral Cavity Personalized Survivor Care Plan for Oral Cancer Patients-Effects on Physical-Psychological Functions and Return-to-Work Dental Hygienists and Dentists as Providers of Oral Mucosa Screening and Brush Biopsies Effects of Mouth-opening Training on the Maximum Interincisal Opening Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer Oral State of Patients Affected by an Oral Cancer Before and After Radiotherapy – 3-years Prospective Study Erlotinib Prevention of Oral Cancer (EPOC) Oral Cancer Screening in Mumbai, India by Primary Health Care Workers Study on the Carcinogenesis of Gα12 in Oral Cancer, and the Treatment of Oral Cancer Using Ga12 Inhibitor. The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor Study on the Carcinogenesis of SOX-9 in Oral Cancer, and Chemopreventive Possibility for the Treatment of Oral Cancer. Validation of DNA Methylation Biomarkers for Oral Cancer Detection Validation of DNA Methylation Biomarkers for Oral Cancer Detection-Follow up Study Rehabilitation Outcomes of Shoulder Function in Oral Cancer Survivors Cancer Survivors Behavior Change on Oral Cancer Patients After a Localized Behavior Change Model Intervention Expression of VEGF-C and VEGF-CR in Oral Cancers and Premalignant Lesions PET/CT and Sentinel Node in Oral Cancer Validation of DNA Methylation Biomarkers for Oral Cancer Detection Web-based Education on Oral Cancer for Primary Care Physicians in Ohio Analysis Of Sensory Recovery Of Donor Size And Quality Life In Oral Cancer Patients Using an APP in Post Oral Cancer Surgery to Affect Patients’ Needs and Quality of Life.

Brief Title

Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions

Official Title

Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions: A Randomized Clinical Trial (Part 1)

Brief Summary

      Oral squamous cell carcinomas (OSCCs) are among the most common types of head and neck
      cancers and are a major cause of significant morbidity. It was reported that 16- 62% of OSCCs
      develop from premalignant lesions, which often presents clinically as white or red mucosal
      patches known as leukoplakia and erythroplakia.

      The role of miRNA in cancer has been established by many studies that have shown that miRNA
      signatures (i.e., mRNA expression profiles) can be useful for classifying human cancers.
      These studies have identified "cancer related miRNAs through investigating expression
      profiles in matched normal and tumor tissues, as well as in body fluids.

      Metformin, one of most widely prescribed oral hypoglycemic agents, has recently received
      increased attention because of its potential anti-tumorigenic effects that are thought to be
      independent of its hypoglycemic effects. Evans et al. first found an association between
      metformin use and decreased cancer incidence.

      The study will reveal whether Systemic Metformin hydrochloride treatment given to patients
      with oral potentially malignant lesions improve the prognosis and prevent or at least reduce
      the incidence of malignant transformation?

Detailed Description

      The idea of identifying oral lesions with a precancerous nature, that is, in the sense of
      pertaining to a pathologic process with an increased risk for future malignant development,
      of course, is to prevent frank malignancy to occur in the affected area.

      In 2005, WHO categorized any lesion or condition that may increase the risk of malignant
      transformation as an 'oral potentially malignant disorder' (OPMD). Early detection of cancer
      development from oral premalignant lesions (OPLs) plays an important role in successful
      therapy. The management of OPMDs varies according to the type of lesion and often differs
      between treatment centers. However, it remains unclear if excision of
      leukoplakia/erythroplakia protects patients against the development of OSCC and no randomized
      controlled trials have been performed to address this issue.

      Various treatment modalities, such as systemic therapies and surgical removal, have been
      suggested. The systemic therapies tested so far include retinoids, extracts of green tea,
      inhibitors of cyclooxygenase-2 and of epidermal growth factor, and peroxisome
      proliferator-activated receptor-c agonists, but there is no generally approved standard
      systemic therapy regimen so far.

      Local removal includes photodynamic therapy, laser therapy, cryotherapy and conventional
      removal by scalpel, but no treatment has so far gained universal approval, no treatment has
      so far been subjected to a randomized clinical trial (RCT), and no treatment has been shown
      to prevent recurrence or significantly reduce malignant development in long-term follow-up
      studies. It is well established that no treatment results in malignant development at an
      annual rate of 2-3%.

      The overall purpose of treatment therefore is to reduce this percentage. However, the
      situation is to take responsibility for the welfare of the patients still is, as it has been
      so far: despite treatment, in some types of lesions cancers do occur, so the important
      question is whether the harm to patients by not treating or by treating them? Lack of
      randomized clinical trials accounts for this persistent question, and while waiting for such
      studies to be reported, it is necessary to reflect on the existing scenarios.

      Field cancerization To explain why surgery may not always be beneficial, it has been
      mentioned that the visible lesions may be surrounded by genetically altered, cancer
      stigmatized epithelial cells unrevealed by routine clinical inspection and histological
      examination. A possible outcome of such characteristics is obviously lacking resection of all
      affected tissue with recurrence and development of carcinoma from residual genetically
      altered cells.

      Introduction to MicroRNA MicroRNAs (miRNAs) are non-coding regulatory RNA molecules of 19-25
      nucleotides in length. miRNAs play a major role in maintaining tissue homeostasis by
      regulating many processes such as cellular proliferation, differentiation, migration,
      apoptosis, survival and morphogenesis.

      It is estimated that the human genome may harbor up to 1,000 miRNAs. Although miRNAs are not
      directly involved in encoding proteins, they are believed to control the expression of more
      than one third of all protein coding genes present within the human genome. Historically,
      miRNAs have been viewed as negative regulators of gene expression. Recent work by Vasudevan
      et al., has, however, shown that a small subset of miRNAs within the human genome can also
      enhance gene expression.

      Role of miRNAs in cancer The role of miRNA in cancer has been reiterated and established by
      many studies that have shown that miRNA signatures (i.e., mRNA expression profiles) can be
      useful for classifying human cancers. These studies have identified "cancer related miRNAs"
      through investigating expression profiles in matched normal and tumor tissues, as well as in
      body fluids. In addition, a vast number of studies have shown that miRNAs can play a role in
      regulating the expression of oncogenes and tumor suppressor genes, whereas others have shown
      that miRNA gene deletion or mutation can lead cancer initiation, progression and metastasis.
      Calin et al., were the first to demonstrate that a differential expression of miRNAs may
      provide useful tools in the diagnosis and prognosis of human cancers.

      MicroRNAs as diagnostic tools Many miRNAs are uniquely and differentially expressed in
      certain tissues as compared with normal adjacent tissues. These small RNA molecules can have
      diagnostic or prognostic value, as miRNA expression profiles reflect tumor origin, stage, and
      other pathological factors. For example, the expression of miRNA let-7 is downregulated in
      lung cancer but not in other cancers, such as breast or colon cancer. These observations
      suggest that miRNAs can be used as biomarkers and diagnostic tools for cancer detection.
      Moreover, miRNAs can function as accurate molecular markers also because they are relatively
      stable and resistant to RNase degradation-probably due to their small size.

      miR-21 and miR-200 seem to be particularly relevant to OSCC. Inhibition of miR-21 in tongue
      cancer cells in vitro reduces survival and anchorage-independent growth. miR-21 increases
      proliferation, migration and anchorage-independent growth of HNSCC cells in vitro and in
      mouse models, thereby augmenting the oncogenic potential of these cells.

      Detection of miRNAs in body fluids With the advances of molecular biological techniques and
      the increasing knowledge of tumor pathogenesis, bio-markers are now considered as an
      effective supplement, in conjunction to histological examination, for facilitating clinical
      decision making. Extracellular miRNAs in serum, plasma, saliva and urine have recently been
      shown to be associated with various pathological conditions, including cancer. Most of the
      circulating miRNAs are included in lipid or lipoprotein complexes, such as apoptotic bodies,
      micro vesicles or exosomes, rendering them inaccessible to degradation by RNAses. Lawrie and
      colleagues were the first to observe elevated levels of miRNA-21 in serum samples collected
      from large B-cell lymphoma patients.

      Explanation for choice of comparators:

      Control/comparator : Patients receiving the standard of care together with PLACEBO starch

      Management strategies for patients with OPLs fall into three categories: close observation,
      surgical removal and ablation, and medical therapies. The mainstay of therapy is observation
      using frequent clinical examinations. The frequency of examinations should be tailored to
      individual patient factors such as the clinical appearance and stage of lesion; presence of
      dysplasia; continued use of tobacco, alcohol, or Areca quid; reliability; and access to
      medical care.

Study Phase

Phase 3

Study Type


Primary Outcome

Clinical Outcomes

Secondary Outcome

 Immunohistochemical analysis


Oral Cancer


Metformin Hydrochloride 500 MG

Study Arms / Comparison Groups

Description:  Metformin hydrochloride tablets 500 mg taken orally once daily for 3 months


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

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

October 1, 2018

Completion Date

September 30, 2020

Primary Completion Date

September 30, 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Both genders with age range from 20 to 70 years.

          -  Patients able to return for the follow up visits and can perform oral hygiene

          -  Clinically diagnosed and histologically confirmed as having oral potentially malignant
             lesions (Atrophic oral lichen planus, leukoplakia, erythroplakia and oral submucous

          -  Patients agreed to sign a written consent after understanding the nature of the study

          -  Patients have diagnosed oral premalignant lesion/lesions and not yet turned into

        Exclusion Criteria:

          -  Diabetic patients (Diabetes Mellitus Type I & II)

          -  Patients have cardiovascular, lung, Renal, Liver diseases

          -  Patients on H2 blocker & proton pump inhibitors therapy as Ranitidine (affects
             metformin absorption and clearance)

          -  Those with allergy or sensitivity to Metformin therapy or having any contraindication
             for their use.

          -  Systemic and/or local systemic drug therapy within the last 3 months prior to the
             start of the study

          -  Patients on steroidal or Non-steroidal anti-inflammatory drugs (NSAIDs) for at least
             the last 6 months

          -  Patients on Antibiotics treatment for at least the last 2 months

          -  Patients on Retinoid, green tea supplements or another natural products therapy

          -  Patients with already diagnosed malignant lesion/lesions

          -  Pregnant or Lactating females

          -  Vulnerable groups as prisoners, mentally disabled, etc…




20 Years - 70 Years

Accepts Healthy Volunteers



, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Cairo University

Study Sponsor

, , 

Verification Date

September 2018