Metformin And Longevity

Prostate Cancer Clinical Trial

— METAL  

Official title:

METformin And Longevity (METAL): A Window of Opportunity Study Investigating Biological Effects of Metformin in Localised Prostate Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02511665
• Other study ID #: METAL
• Status: Not yet recruiting
• Phase: Phase 4
• First received: July 27, 2015
• Last updated: July 29, 2015
• Start date: July 2015
• Est. completion date: July 2017

Study information

• Verified date: July 2015
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This is a randomized, placebo-controlled, double-blind, window of opportunity study investigating the biological mechanism of metformin in prostate cancer.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 185
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Metformin
Given metformin

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

Locations

Country	Name	City	State
United Kingdom	Guy's Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust	King's College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms.		24 months	No