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Metformin And Longevity (METAL)

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ClinicalTrials.gov Identifier: NCT02511665
Recruitment Status : Unknown
Verified July 2015 by Guy's and St Thomas' NHS Foundation Trust.
Recruitment status was:  Not yet recruiting
First Posted : July 30, 2015
Last Update Posted : July 30, 2015
Sponsor:
Collaborator:
King's College London
Information provided by (Responsible Party):
Guy's and St Thomas' NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE July 27, 2015
First Posted Date  ICMJE July 30, 2015
Last Update Posted Date July 30, 2015
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2015)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Metformin And Longevity
Official Title  ICMJE METformin And Longevity (METAL): A Window of Opportunity Study Investigating Biological Effects of Metformin in Localised Prostate Cancer
Brief Summary This is a randomized, placebo-controlled, double-blind, window of opportunity study investigating the biological mechanism of metformin in prostate cancer.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Metformin
    Given metformin
    Other Name: Glucophage
  • Radiation: PET-MRI Scan
    Patients will under go 2 PET-MRI scans in the PET-MRI substudy arm one before treatment with metformin and one after
  • Drug: Placebo
    Given placebo
Study Arms  ICMJE
  • Experimental: Metformin
    Metformin given , 1g twice a day for 4 weeks until prostatectomy +/- one week
    Intervention: Drug: Metformin
  • Placebo Comparator: Placebo
    placebo given , 1g twice a day for 4 weeks until prostatectomy +/- one week
    Intervention: Drug: Placebo
  • 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
    Intervention: Radiation: PET-MRI Scan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: July 29, 2015)
185
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2017
Estimated Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 18 or older and willing and able to provide signed informed consent.
  2. Histologically confirmed adenocarcinoma of the prostate , with a minimum maximal tumour length of greater than 6mm on core biopsy
  3. No previous treatment for prostate cancer (including surgery, any hormone therapy, radiotherapy and cryotherapy)
  4. 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..
  5. Radical prostatectomy is the scheduled treatment of choice
  6. Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 0 or 1.
  7. 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
  8. Able to swallow the drug and comply with study requirements.

Exclusion Criteria:

  1. Patients with a current or historical diagnosis of type one or two Diabetes and/or have ever received metformin
  2. Patients with hypersensitivity to any of the components of Metformin or placebo tablet
  3. History of or conditions associated with lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), and conditions associated with hypoxaemia
  4. 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)
  5. Patients with acute severe disorders, for example infections with fever, pancreatitis, trauma, dehydration or reduced diet (<1000kcal or 4200kJ per day)
  6. 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)
  7. Current enrolment in an investigational drug or device study or participation in such a study within 30 days of signing consent.
  8. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02511665
Other Study ID Numbers  ICMJE METAL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guy's and St Thomas' NHS Foundation Trust
Study Sponsor  ICMJE Guy's and St Thomas' NHS Foundation Trust
Collaborators  ICMJE King's College London
Investigators  ICMJE
Principal Investigator: Sarah Rudman, MBBS BSc PhD Guy's and St Thomas NHS Trust
PRS Account Guy's and St Thomas' NHS Foundation Trust
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP