M4OC-Prevent: Metformin for Oral Cancer Prevention
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Clinical Response to Metformin Intervention
研究概览
简要总结
This phase IIa trial studies how well metformin hydrochloride works in preventing oral cancer in patients with an oral premalignant lesion (oral leukoplakia or erythroplakia). Oral premalignant lesions look like red or whitish plaques or lesions in the mouth that do not rub off and can be associated with a higher risk of cancer. Metformin hydrochloride may help prevent oral cancer from forming in patients with an oral premalignant lesion.
详细描述
PRIMARY OBJECTIVES:
I. To determine the clinical response of oral premalignant lesions to 12-14 weeks of metformin (metformin hydrochloride) intervention.
SECONDARY OBJECTIVES:
I. Histologic response to metformin intervention in the target lesion. II. Tissue-based biomarkers: metformin effect on cell proliferation and its molecular targets in the target lesion and in the normal tissue (marker of cell proliferation, Ki67, molecular targets of metformin, including, in order of priority, phosphorylated ribosomal protein S6 kinase [pS6], phosphorylated v-akt murine thymoma viral oncogene homolog 1 [pAKT]S473, phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 [p4EBP], phosphorylated acetyl-CoA carboxylase alpha [pACC]).
III. Tissue-based biomarkers: expression of dysregulated molecular mechanisms and organic cation transporter 3 (OCT 3) in the target lesion and in the normal tissue, including, in order of priority, epidermal growth factor receptor (EGFR), phosphorylated (p)EGFR, tumor protein 53 (p53), phosphatase and tensin homolog (PTEN), phosphorylated mitogen-activated protein kinase 1 (pERK), cyclin-dependent kinase inhibitor 2A (p16), and OCT3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia, or hyperplasia not associated with mechanical factors such as ill-fitted dentures
- •Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy
- •Karnofsky performance status >= 70%
- •Leukocytes >= 3,000/microliter
- •Absolute neutrophil count >= 1,000/microliter
- •Platelets >= 100,000/microliter
- •Total bilirubin =< 1.5 × institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =<1.5 × institutional ULN
- •eGFR > 40 mL/min using the Cockcroft-Gault equation
- •Life expectancy > 3 months
- •Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation
- •Ability to take oral medication
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patients with diabetes who are taking insulin or oral agents
- •History of diabetic ketoacidosis
- •Participants may not be receiving any other investigational agents within past 3 months
- •History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, human immunodeficiency virus (HIV)-positive, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Oral carcinoma in situ
- •History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months; b) consumption of 7 or more alcoholic beverages within a 24 hour (hr) period in the past 12 months
- •Glycated hemoglobin (HbA1c) > 8%
- •Pregnancy or nursing women
- •Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension
- •History of renal disease
- •History of prior head and neck squamous cell carcinoma (HNSCC) unless curatively treated for >= 1 year
- •Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 2 years; ongoing adjuvant hormonal therapy for breast cancer is allowed
研究组 & 干预措施
Prevention (extended-release metformin hydrochloride)
Patients receive extended-release metformin hydrochloride PO QD for 2 weeks and then BID for 10-12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Prevention (extended-release metformin hydrochloride)
Patients receive extended-release metformin hydrochloride PO QD for 2 weeks and then BID for 10-12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Metformin Hydrochloride (Drug)
结局指标
主要结局
Clinical Response to Metformin Intervention
时间窗: Baseline to up to 14 weeks
Number of participants with complete and partial clinical response to metformin intervention. Criteria for complete and partial clinical response are: Complete Response (CR): Disappearance of all evidence of lesion(s). Partial Response (PR): Greater than or equal to 50% reduction in the sum of the products of diameters of lesion(s) measurable at baseline. Non-measurable lesion(s) may not increase greater than or equal to 25% in size and no new lesion may appear.
次要结局
- Histologic Response to Metformin Intervention(Baseline to up to 14 weeks)
- Changes in Frequent Dysregulated Molecular Mechanisms and OCT Expression(Baseline to up to 14 weeks)
- Impact of Genomic Alterations on the Biological and Biochemical Consequences and Clinical Response to Metformin Hydrochloride(Up to 14 weeks)
- Change in Measurements of Metformin Hydrochloride Concentrations in Serum and Saliva(Baseline to up to 14 weeks)
- Changes in Cell Proliferation and Its Molecular Targets(Baseline to up to 14 weeks)
- Change in Serum and Saliva Inflammatory and Angiogenic Cytokines(Baseline to up to 14 weeks)
- Change in Serum Metabolic Markers(Baseline to up to 14 weeks)