Ignite Creation Date:
2024-05-06 @ 2:11 AM
Last Modification Date:
2024-10-26 @ 11:14 AM
Study NCT ID:
NCT01981525
Status:
COMPLETED
Last Update Posted:
2020-12-14
First Post:
2013-11-07
Brief Title:
A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome
Status:
COMPLETED
Status Verified Date:
2020-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed Description:
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 8 14 and 20
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 8 14 and 20
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 14-C-0005 | None | None | None |