METformin And Longevity (METAL): A Window of Opportunity Study Investigating Biological Effects of Metformin in Localised Prostate Cancer
试验速览
- 阶段
- 4 期
- 入组人数
- 185
- 试验地点
- 1
- 主要终点
- Assessment of the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms.
研究概览
简要总结
This is a randomized, placebo-controlled, double-blind, window of opportunity study investigating the biological mechanism of metformin in prostate cancer.
详细描述
A potential role for metformin in prostate cancer has been suggested and given its wide availability, tolerable side effect profile and safety record it may represent a therapeutic option for men with prostate cancer. However, the mechanism of action by which metformin exerts its anti-cancer effect has yet to be fully characterised. This 'window of opportunity' trial provides an opportunity to investigate this by comparing baseline prostate biopsies with post-treatment surgical specimen by focussing on assessment of the FASN/AMPK axis.
Patients with newly-diagnosed, early stage, prostate cancer scheduled for radical prostatectomy will either enter the main study and be randomised 1:1 to receive metformin (2g daily over 2 divided doses; Arm A) or placebo four weeks prior to prostatectomy (standard of care; Arm B). Or a subset of five patients will enter the exploratory PET-MRI Substudy . These five patients will all receive metformin and will undergo an additional two PET-MRI Scans.
Prostate tissue (at baseline from biopsy and post treatment from prostatectomy) will be used for analysis of p-AMPK, p-ACC, FASN by immunohistochemistry and proliferation will be measured using Ki67 and TUNEL in both metformin and placebo groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age 18 or older and willing and able to provide signed informed consent.
- •Histologically confirmed adenocarcinoma of the prostate , with a minimum maximal tumour length of greater than 6mm on core biopsy
- •No previous treatment for prostate cancer (including surgery, any hormone therapy, radiotherapy and cryotherapy)
- •Prostate biopsy within 8 weeks from screening which contains sufficient material for baseline molecular marker assessment at Guy's and St Thomas' NHS Foundation trust..
- •Radical prostatectomy is the scheduled treatment of choice
- •Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 0 or
- •Adequate organ function, defined as follows:
- •Haemoglobin >10.0g/dL
- •Absolute neutrophil count >1.5x109/L
- •Platelet count >100x109/L
- •Renal function, eGFR >60ml/min (calculated by Cockcroft Gault)
- •AST and/or ALT <2.5 x ULN
- •Total Bilirubin <1.5 x ULN
- •Able to swallow the drug and comply with study requirements.
排除标准
- •Patients with a current or historical diagnosis of type one or two Diabetes and/or have ever received metformin
- •Patients with hypersensitivity to any of the components of Metformin or placebo tablet
- •History of or conditions associated with lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), and conditions associated with hypoxaemia
- •Patients with chronic liver disease, severe cardiovascular impairment, cardiac failure, recent myocardial infarction, severe peripheral vascular disease or renal impairment (eGFR <60ml/min as measured by Cockcroft Gault)
- •Patients with acute severe disorders, for example infections with fever, pancreatitis, trauma, dehydration or reduced diet (<1000kcal or 4200kJ per day)
- •Other active malignancy over the last five years that has required systemic therapy, excluding:
- •Adjuvant therapy in the curative setting
- •Non-melanoma skin cancer
- •Superficial transitional cell carcinoma (CIS-T1)
- •Current enrolment in an investigational drug or device study or participation in such a study within 30 days of signing consent.
- •Any subjects who is able to father a child and does not agree to use barrier protection, in the form of a condom ,for the duration of the trial and for 16 weeks after the last study drug administration.
研究组 & 干预措施
Placebo
placebo given , 1g twice a day for 4 weeks until prostatectomy +/- one week
干预措施: Placebo (Drug)
Metformin
Metformin given , 1g twice a day for 4 weeks until prostatectomy +/- one week
干预措施: Metformin (Drug)
PET-MRI
5 patients in this arm will all receive metformin and undergo two additional PET- MRI scans, one before and one after treatment
干预措施: PET-MRI Scan (Radiation)
结局指标
主要结局
Assessment of the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms.
时间窗: 24 months
次要结局
未报告次要终点