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Metformin And Longevity (METAL)

Primary Purpose

Prostate Cancer

Status
Unknown status
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Metformin
PET-MRI Scan
Placebo
Sponsored by
Guy's and St Thomas' NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Guy's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Metformin

Placebo

PET-MRI

Arm Description

Metformin given , 1g twice a day for 4 weeks until prostatectomy +/- one week

placebo given , 1g twice a day for 4 weeks until prostatectomy +/- one week

5 patients in this arm will all receive metformin and undergo two additional PET- MRI scans, one before and one after treatment

Outcomes

Primary Outcome Measures

Assessment of the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms.

Secondary Outcome Measures

Full Information

First Posted
July 27, 2015
Last Updated
July 29, 2015
Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London
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1. Study Identification

Unique Protocol Identification Number
NCT02511665
Brief Title
Metformin And Longevity
Acronym
METAL
Official Title
METformin And Longevity (METAL): A Window of Opportunity Study Investigating Biological Effects of Metformin in Localised Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Unknown status
Study Start Date
July 2015 (undefined)
Primary Completion Date
July 2017 (Anticipated)
Study Completion Date
July 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
185 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metformin
Arm Type
Experimental
Arm Description
Metformin given , 1g twice a day for 4 weeks until prostatectomy +/- one week
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo given , 1g twice a day for 4 weeks until prostatectomy +/- one week
Arm Title
PET-MRI
Arm Type
Experimental
Arm Description
5 patients in this arm will all receive metformin and undergo two additional PET- MRI scans, one before and one after treatment
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Intervention Description
Given metformin
Intervention Type
Radiation
Intervention Name(s)
PET-MRI Scan
Intervention Description
Patients will under go 2 PET-MRI scans in the PET-MRI substudy arm one before treatment with metformin and one after
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Given placebo
Primary Outcome Measure Information:
Title
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

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarah Rudman, MBBS BSc PhD
Organizational Affiliation
Guy's and St Thomas NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danielle Crawley, MBBS
Phone
02071887904
Email
danielle.crawley@kcl.ac.uk

12. IPD Sharing Statement

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Metformin And Longevity

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