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

NCT01981525 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 26

Last updated 2020-12-14

No results posted yet for this study

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.

Conditions

  • Li-Fraumeni Syndrome

Interventions

DRUG

Metformin

Treatment will be administered primarily on an outpatient basis. Patients will be instructed to take 500 mg metformin by mouth 1, 2 or 3 times a day or 1000 mg twice per day depending on dose level. Patients will receive metformin at level 1 dose for 2 weeks. If dose is tolerated, patient will receive level 2 dose for 2 weeks and if tolerated will escalate to level 3 dose, and if tolerated will escalate to level 4 dose. Metformin will be taken for 14 weeks.

Sponsors & Collaborators

  • National Cancer Institute (NCI)

    lead NIH

Principal Investigators

  • Christina M Annunziata, M.D. · National Cancer Institute (NCI)

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-01-27
Primary Completion
2016-06-30
Completion
2020-12-11
FDA Drug
Yes

Countries

  • United States

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01981525 on ClinicalTrials.gov