MRC Clinical Trials Unit at UCL
90 High Holborn
a. Is liquid metformin permitted?
Yes, any formulation of metformin is permitted providing one of the dose schedules stated it the STAMPEDE protocol are followed. All patients should aim to receive the target dose of 850mg BD. Please refer to protocol section 6.2.6 for further details.
b. What to do if a patient develops a macrocytic anaemia whilst on metformin?
Check haematinics including vitamin B12 as deficiency is a recognised side effect of metformin. Start replacement therapy if deficiency is confirmed, metformin may continue.
c. Is dose escalation allowed post 4 weeks?
Yes, all patients should attempt a dose escalation to the target dose of 850mg BD providing the starting dose is reasonably well tolerated. Dose escalation should be attempted around 4-6 weeks post treatment starting but can be attempted at any time point. If a dose escalation is not attempted the reason why should be clearly documented.
d. What is the advice on alcohol consumption and metformin?
The reference safety information for metformin advises against metformin use in individuals with excessive alcohol intake as this is a risk factor for lactic acidosis. Reasonable alcohol intake is safe. Metformin should not be given in individuals with alcohol dependency.
e. When should patients stop taking metformin?
Patients with metastatic disease at trial entry should continue on metformin whilst on ADT and post progression i.e. lifelong providing it is judged to be in the patients’ best interest.
Patients with non-metastatic disease should continue also continue metformin whilst on ADT. If ADT is stopped after the minimum of 2 years, metformin should continue for a further 12 months i.e. 3 years. If metformin is stopped 12 months after last administration of LHRH, it should not be re-started in the event of relapse.
f. How to label metformin bottles prescribed to patients allocated to arm K?
All Arm K stock will require additional trial-specific labelling by the site pharmacist before dispensing. Pharmacies are required to have a written SOP in place for trial-specific labelling procedures. Template labels are available on the STAMPEDE website, further information may be added to the labels but nothing should be omitted.
g. How to document accountability and destruction of metformin tablets?
No template destruction or accountability logs are provided. Pharmacies must use local templates for Arm K supplies.
h. Can metformin be couriered to a patient?
For accountability reasons, STAMPEDE related treatment drugs cannot be posted to patients.
i. Should pharmacies inform the STAMPEDE unit each time their brand of metformin changes?
No, this is not necessary as long as the batch number is appropriately recorded for each dispensed visit and is able to be traced to the brand of metformin that was dispensed.
j. A patient has progressed and is starting second line treatment, should metformin stop?
No, metformin should continue for as long at the patient is receiving ADT. Metformin can be safely given with all treatments given for disease progression.
k. A patient is being considered for a second line CTIMP in castrate resistant prostate cancer, should being on continued metformin affect his participation?
It is not usually permitted for patients to receive two IMPs at once. If the treating medical team believe it would be in the best interest of the patient to join a second line trial, metformin should be stopped.
l. A patient is attending hospital for a CT scan, does metformin need to be paused?
If the GFR is <60 ml/min/1.73m2 metformin should be paused for 24 hours prior to receiving contrast and re-started 48 hours post‑administration.
m. What drugs are contra-indicated for patients receiving metformin?
Caution is needed when starting any medications that may be potentially nephrotoxic due to the risk of reduced metformin clearance. This includes non-steroidal anti-inflammatories such as naproxen, diclofenac and ibuprofen, anti-hypertensives such as ACE inhibitors, diuretics and certain intravenous antibiotics. Metformin can be safely given with all prostate cancer treatments that may be given after disease progression and should continue where possible.
n. A patient has been admitted for a procedure and has worsening urinary outcome and renal function, should metformin be permanently stopped?
Metformin should be paused in any scenario where there is a risk of deteriorating renal function. If the eGFR falls to less than 30 ml/min/1.73m2 and does not recover metformin must be permanently stopped.
o. A patient has developed diabetes after being randomised to Arm K, how should this be managed?
Diabetes should be managed according to the treating clinician and any changes to the metformin dose should be documented on the metformin treatment log. The patient can remain on STAMPEDE follow-up as per normal.
Have another question or looking for more information? why not check out the STAMPEDE Training Suite for the training slides detailing information on STAMPEDE.
MRC Clinical Trials Unit at UCL