CompletedPhase 1

A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome

United States26 participantsStarted 2014-01-27

Plain-language summary

Background: * Li Fraumeni Syndrome (LFS) is a highly penetrant, autosomal dominant cancer predisposition disorder. Four main cancer types including sarcoma, adrenocortical carcinoma, breast cancer, and malignant brain tumors commonly characterize LFS but the syndrome can include other cancers. * Metformin is an oral biguanide drug that is approved by the FDA for the treatment of type II diabetes. Metformin has been associated with reduced cancer risk in several epidemiologic studies and reduced cancer mortality in patients with type 2 diabetes. * Metformin decreases circulating insulin and IGF1, and promotes glucose uptake in skeletal muscle and inhibits gluconeogenesis in the liver. Elevations in circulating insulin and IGF1 levels have been associated with increased cancer risk. * Preclinical research in animal models shows that metformin may be more toxic in cancer cells that have lost p53 function. * Lifetime risk of cancer in LFS patients with germline TP53 mutations is estimated to be up to 70% by age 60, with women having excess lifetime cancer risk (up to 100%) compared to men (up to 80%). There are currently no approved chemopreventive agents for patients with LFS. * Metformin has been shown to be safe and tolerable in diabetic and non-diabetics, and may be an ideal candidate for chemoprevention of cancer in this population. Objectives: * Determine the tolerability of oral daily metformin in patients with LFS caused by germline TP53 mutations. * Determine if 8 weeks of daily metformin administration has any effect on circulating IGF-1, insulin, and IGFBP3 Eligibility: * Must have a germline TP53 mutation and provide documentation of testing. * Must have adequate organ function. * Age greater than or equal to 18 years. Design: * This is a pilot study to assess the tolerability of daily oral metformin administration in patients with LFS caused by germline TP53 mutations and to study the effect of metformin on biomarker levels in these subjects. * In the absence of intolerable toxicity, a minimum of 22 patients will take metformin by mouth for a total of 14 weeks and then discontinue metformin for 6 weeks. The total time on study will be 20 weeks. * Patients will be assessed for biomarker levels (IGF-1, insulin, IGFBP3) by blood sample at baseline, and weeks 0 and 8.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

* INCLUSION CRITERIA: * All TP53 germline mutation positive adult patients will be eligible for this study. All patients must have a documented TP53 germline mutation. * Patients with history of cancer must be in remission, with surgery completed at least 6 months prior to enrollment and chemotherapy completed at least 1 year prior to enrollment (except for basel cell carcinoma of the skin). * Age greater than or equal to 18 years. The doses of metformin used in this study exceed the maximum recommended daily dose for the pediatric population. * ECOG performance status 0 or 1 or Karnofsky greater than or equal to 70% * Patients must have normal organ and marrow function as defined below: * Leukocytes\*: greater than or equal to 3,000/microL\* * Absolute neutrophil count: greater than or equal to 1,500/ microL * Platelets: greater than or equal to 100,000/ microL * Total bilirubin: Within normal institutional limits * AST(SGOT) / ALT(SGPT): less than or equal to 2.5 times institutional upper limit of normal * Creatinine: Within normal institutional limits OR * Creatinine clearance: greater than or equal to 60 mL/min/1.73m(2) if serum creatinine \> institutional normal * Note: If leukopenia is idiopathic and no other significant co-morbidities exist patients will not be excluded on the basis of their WBC. * Metformin is a category B drug and can be used to treat gestational diabetes. Levels of metformin excreted in breast milk appear to be low and not clinic…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Determine the tolerability of metformin in patients with LFS caused by germline TP53 mutations

Timeframe: 2 years

Determine if 8 weeks of daily metformin administration has any effect on circulating IGF-1, insulin, and IGFBP3

Timeframe: 2 years

Trial details

NCT IDNCT01981525

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2016-06-30

View on ClinicalTrials.gov More Li-Fraumeni Syndrome trials