Metformin And Longevity

Phase 4

• Conditions: Prostate Cancer
• Interventions: Drug: Placebo; Radiation: PET-MRI Scan; Drug: Metformin

• Registration Number: NCT02511665
• Lead Sponsor: Guy's and St Thomas' NHS Foundation Trust

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 Timeline

• Status Verified: 2015-07
• Study Start: 2015-07
• Study First Submitted: 2015-07-27
• Study First Submitted QC: 2015-07-29
• Last Update Submitted: 2015-07-29
• Study First Posted: 2015-07-30
• Last Update Posted: 2015-07-30
• Primary Completion: 2017-07
• Study Completion: 2017-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 185

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	placebo given , 1g twice a day for 4 weeks until prostatectomy +/- one week
PET-MRI	PET-MRI Scan	5 patients in this arm will all receive metformin and undergo two additional PET- MRI scans, one before and one after treatment
Metformin	Metformin	Metformin given , 1g twice a day for 4 weeks until prostatectomy +/- one week

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Guy's Hospital; 🇬🇧 London, United Kingdom