- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02511665
Metformin And Longevity (METAL)
METformin And Longevity (METAL): A Window of Opportunity Study Investigating Biological Effects of Metformin in Localised Prostate Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
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London, United Kingdom, SE1 9RT
- Guy's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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 1.
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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Metformin
Metformin given , 1g twice a day for 4 weeks until prostatectomy +/- one week
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Given metformin
Other Names:
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Placebo Comparator: Placebo
placebo given , 1g twice a day for 4 weeks until prostatectomy +/- one week
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Given placebo
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Experimental: PET-MRI
5 patients in this arm will all receive metformin and undergo two additional PET- MRI scans, one before and one after treatment
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Patients will under go 2 PET-MRI scans in the PET-MRI substudy arm one before treatment with metformin and one after
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Assessment of the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms.
Time Frame: 24 months
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24 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Sarah Rudman, MBBS BSc PhD, Guy's and St Thomas NHS Trust
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- METAL
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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