A clinical trial investigating the use of a drug called metformin as a way of reducing the cancer risk in people with Li Fraumeni Syndrome (LFS)

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 224

Inclusion Criteria

1. Diagnosis of LFS from confirmed pathogenic TP53 variant (class IV or V by CanVIG-UK criteria
2. Aged >16 years
3. Capable of understanding the consent process and participating in the study (including proving blood samples), in the investigators’ decision

Exclusion Criteria

1. Currently taking metformin
2. Metformin intake for more than 3 months in total, within the 2 years antecedent to the date of trial enrolment
3. Completion of cancer systemic therapy within the 6 months antecedent to the date of trial enrolment
4. Current type 1 or 2 diabetes mellitus
5. Presence of ongoing active cancer (detected previously or at baseline scanning)
6. Current pregnancy or lactation
7. Gastro-intestinal condition (such as short-bowel syndrome) that could affect uptake of metformin
8. Concurrent illness (other than LFS) that could result in life expectancy of <5 years
9. History of the following cardiac conditions:
9.1. Congestive cardiac failure of >Grade II severity according to the New York Heart Association Functional Classification (defined as symptomatic at less than ordinary levels of activity).
9.2. Ischaemic cardiac event including myocardial infarction within 3 months prior to date of enrolment.
9.3. Uncontrolled cardiac disease,including unstable angina pectoris,uncontrolled hypertension (i.e.,sustained systolic BP >160 mmHg or diastolic BP >90 mm Hg)
10. Evidence of significant renal impairment eGFR <50ml50ml/minute/1.73m² (those with eGFR between 50-60ml/minute/1.73m² are eligible to enter but, if in the metformin arm, will undergo modified dose-titration)
11. Liver cirrhosis and/or alkaline phosphatase,aspartate transaminase or alanine transaminase >2.5 x upper limit of normal (ULN)
12. Elevated risk of lactic acidosis such as current chronic alcoholism,congenital lactic acidosis,concurrent intake of carbonic anhydrase inhibitor (e.g. acetazolamide)
13. Known allergy to metformin
14. Does not fulfil MRI Safety Screening criteria (e.g. implanted cardiac pacemaker, post-surgical metal hardware – plates etc) and/or unable to undergo baseline scan.