Metformin And Longevity

NCT ID: NCT02511665

Last Updated: 2015-07-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 185 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-07-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

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

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Given metformin

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Given placebo

PET-MRI

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

Group Type: EXPERIMENTAL

PET-MRI Scan

Intervention Type: RADIATION

Patients will under go 2 PET-MRI scans in the PET-MRI substudy arm one before treatment with metformin and one after

Interventions

Metformin

Given metformin

Intervention Type: DRUG

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

Intervention Type: RADIATION

Placebo

Given placebo

Intervention Type: DRUG

Other Intervention Names

Glucophage

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

King's College London

OTHER

Sponsor Role: collaborator

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sarah Rudman, MBBS BSc PhD

Role: PRINCIPAL_INVESTIGATOR

Guy's and St Thomas NHS Trust

Locations

Guy's Hospital

London, , United Kingdom

Countries

United Kingdom

Facility Contacts

Danielle Crawley, MBBS

Role: primary

danielle.crawley@kcl.ac.uk

02071887904

Other Identifiers

METAL

Identifier Type: -

Identifier Source: org_study_id