Li Fraumeni Syndrome Cancer
Conditions
Interventions
Current interventions, as of 08/04/2025:
This is a randomised clinical trial for participants with LFS as per the inclusion criteria below. People with LFS should undergone yearly MRI whole-body, br
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
16 Years to 100 Years
Inclusion criteria
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 providing blood samples), in the investigators’ decision
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 03/06/2026: 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 active ongoing cancer /or currently receiving cancer treatment (excluding maintenance treatments e.g., hormones) 6. Current pregnancy or lactation 7. Gastro-intestinal condition (such as short-bowel syndrome) that would affect absorption of metformin 8. Concurrent illness (other than LFS) that could result in life expectancy 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 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 _____ Previous exclusion criteria as of 01/04/2025: 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 active ongoing cancer /or currently receiving cancer treatment (excluding maintenance treatments e.g., hormones) 6. Current pregnancy or lactation 7. Gastro-intestinal condition (such as short-bowel syndrome) that would affect absorption of metformin 8. Concurrent illness (other than LFS) that could result in life expectancy 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 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. Kn
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cancer free survival – with “cancer” event defined as pathologically confirmed diagnosis of malignant cancer identified during trial participation or death from any cause up to 5 years (60 months) following randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Tumour free survival – with a “tumour” event including pathologically confirmed diagnosis of malignant cancer or clinically/scan detected benign or premalignant lesion (e.g. ductal carcinoma in situ - DCIS) identified during trial participation or death from any cause. Measured by time to development of new cancer and/or benign lesion in each trial arm within 60 months of randomisation and % events. 2. Time from randomisation to death from any cause within 60 months post-group allocation and % events. 3. Number and type of emerging cancers, including size, stage and histological grade at diagnosis measured by number, type and stage of cancer diagnosed within each trial arm within 60 months post-group allocation 4. Relevant treatment-emergent adverse events and clinically significant laboratory changes (per NCI CTCAE v5.0) or changes in physical exam and/or vital signs in investigation arm compared to baseline measured by number of and severity of relevant AEs in metformin trial arm within 60 months post-group allocation 5. MARS-5 questionnaire score in the metformin arm from group allocation to 60 months 6. Change in 12-item short form survey (SF12v2), Cancer Worry Scale, Treatment Burden Questionnaire (TBQ) over 60 months post-group allocation 7. Baseline weight, BMI and lifestyle factors (e.g. smoking and diet) | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactImogen North
Outcome results
None listed