Li-Fraumeni SyndromePhase 1NCT01981525
A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome
A Phase 1 study testing Metformin in people with Li-Fraumeni Syndrome, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Li-Fraumeni Syndrome
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2014to 11 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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*
Show all 23Show fewer
- 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 clinically significant. However, for protocol safety reasons, we will not be enrolling pregnant and/or nursing women in this study as metformin as has not been extensively evaluated in non-diabetic pregnant and nursing women. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women who are nursing will be advised to discontinue breastfeeding if the mother is treated with metformin. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform Drs. Annunziata or Walcott, or protocol physicians/study team at NCI and her primary care provider immediately.
- Ability of subject to understand and the willingness to sign a written informed consent document.
- GENERAL EXCLUSION CRITERIA:
- Patients who have had stem-cell transplantation.
- Current use of metformin or other anti-diabetic agents, or hypersensitivity or allergy to metformin.
- Patients who are receiving any other investigational agents.
- Patients with history of chronic alcohol use
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin or other agents used in study.
- Patients with congestive heart failure requiring pharmacological management.
- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Who cannot join
- Exclusion criteria for 13C-MBT studies in addition to general exclusion criteria (pertaining to effects of oral uptake of the administered substrate or mitochondrial function in the liver):
- Gastric paresis
- Short gut syndrome
- Inflammatory bowel disease*
- Celiac sprue
- Pancreatic insufficiency or disease
Show all 21Show fewer
- Any malabsorption disease/syndrome
- Chronic PPI use or H2 blocker use that cannot be temporarily discontinued (at least 48 hours)
- Any acetaminophen, aspirin, NSAID, or statin use within 2 days of testing (known to affect mitochondrial function)
- Drugs that interfere with mitochondrial function if they are unable to be discontinued 48 hours prior to (13)MBT testing will be excluded for this test only but eligible for the rest of the protocol.
- Any oral steroid use within 2 weeks of testing
- Chronic alcohol use** defined as > 2 standard drinks per day (more than 2 beers, 2 glasses of wine, or 2 shots of liquor per day)
- Inflammatory bowel disease will be exclusion for the (13)C-MBT only, because even if well controlled we do not know the effect chronic inflammation in the bowel and steroid use may have on the test. The test analyzes exhaled CO2 in the breath and this can be affected by diet (carbohydrate heavy), exercise, and certain pathologies like liver disease. Also pro-inflammatory mediators have been shown to cause hepatocellular injury that may also interfere with results of the test.
- The test is currently being studied as an early detection, non-invasive method for liver cirrhosis. Therefore, patients who have had chronic alcohol use consistent with a regular pattern of alcohol consumption may have underlying liver disease that may affect the CO2 measurement. Further, alcohol changes the NADH/NAD ratio intracellularly and studies have shown that alcohol can inhibit methionine oxidation. Previous protocols utilizing the (13)C-MBT have excluded patients who consume greater than 20 g/day of alcohol. A standard drink is equivalent to approximately 14 g/day of alcohol (one 12 oz beer, one 5 oz glass of wine, or one shot of liquor). This information was obtained from the National Institute of Health/National Institute of Alcohol Abuse and Alcoholism (NIAAA):
- http://pubs.niaaa.nih.gov/publications/Practitioner/pocketguide/pocketguide2.htm). We will also evaluate LFTs and should clinical concern arise, check PT/PTT and albumin. Patients with normal liver function and no substantial history of alcohol abuse will be eligible.
- Although patients will need to sign a separate informed consent to undergo the (31)P-MRS studies the list below includes some of the general exclusion criteria as information for the caring physician. Exclusion criteria for (31)P-MRS studies in addition to general exclusion criteria:
- Inability to perform exercise with dominant leg
- Claustrophobia and/or inability to lie flat in MRI machine
- Metal medical implantable device or other MRI incompatible materials
- Body mass index under 19 or over 45
- Prior stem cell transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Li-Fraumeni Syndrome
- Being tested
- Metformin
- Keywords
- TP53 germline mutations
- Medical subject headings
- Li-Fraumeni Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the tolerability of metformin in patients with LFS caused by germline TP53 mutations
toxicity assessment by CTCAE ver 4.0
Measured: 2 years
Determine if 8 weeks of daily metformin administration has any effect on circulating IGF-1, insulin, and IGFBP3
biomarker levels (IGF-1, insulin, IGFBP3) by blood sample at baseline, and weeks 0, 8, 14 and 20
Measured: 2 years
Secondary outcomes (2)
Determine if daily metformin administration has any effect on circulating IGF-1, insulin, and IGFBP3 levels, two weeks after the start of metformin administration and six weeks after discontinuing metformin (week 20)
toxicity classification by NCI Common Terminology Criteria for Adverse Events (CTCAE)
Measured: 2 years
Determine if daily metformin administration has any effect on skeletalmuscle mitochondrial function using phosphorous-31 magnetic resonance spectroscopy (31P-MRS) baseline and eight weeks after the start of metformin.
biomarker levels (IGF-1, insulin, IGFBP3) by blood sample at baseline, and weeks 0, 8, 14 and 20
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2013 (estimated)
- Study start27 Jan 2014
- Primary completion30 Jun 2016
- Study completion11 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Li-Fraumeni SyndromeStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christina M Annunziata, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01981525
- Sponsor's protocol ID
- 140005
- Other IDs
- 14-C-0005
- Status last verified
- Dec 2020
- First submitted
- 7 Nov 2013
- Last updated
- 14 Dec 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Li FP, Fraumeni JF Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 1969 Oct;71(4):747-52. doi: 10.7326/0003-4819-71-4-747. No abstract available.
PubMed 5360287Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988 Sep 15;48(18):5358-62.
PubMed 3409256Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011 Jun;12(6):559-67. doi: 10.1016/S1470-2045(11)70119-X. Epub 2011 May 19.
PubMed 21601526Wang PY, Li J, Walcott FL, Kang JG, Starost MF, Talagala SL, Zhuang J, Park JH, Huffstutler RD, Bryla CM, Mai PL, Pollak M, Annunziata CM, Savage SA, Fojo AT, Hwang PM. Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome. J Clin Invest. 2017 Jan 3;127(1):132-136. doi: 10.1172/JCI88668. Epub 2016 Nov 21.
PubMed 27869650
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome
- ClinicalTrials.gov ID
- NCT01981525
- Acronym / sponsor ID
- 140005
- Conditions
- Li-Fraumeni Syndrome
- Keywords
- TP53 germline mutations
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 27 Jan 2014 (actual)
- Primary completion
- 30 Jun 2016 (actual)
- Study completion
- 11 Dec 2020 (actual)
- First posted
- 11 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: MetforminPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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:
Key exclusion criteria (21 listed)
- Exclusion criteria for 13C-MBT studies in addition to general exclusion criteria (pertaining to effects of oral uptake of the administered substrate or mitochondrial function in the liver):
- Gastric paresis
- Short gut syndrome
- Inflammatory bowel disease*
- Celiac sprue
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminTreatment 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. | Drug | Arm 1 |
Primary outcome
Determine the tolerability of metformin in patients with LFS caused by germline TP53 mutations
Time frame: 2 years
toxicity assessment by CTCAE ver 4.0
Determine if 8 weeks of daily metformin administration has any effect on circulating IGF-1, insulin, and IGFBP3
Time frame: 2 years
biomarker levels (IGF-1, insulin, IGFBP3) by blood sample at baseline, and weeks 0, 8, 14 and 20
2 secondary outcomes
Determine if daily metformin administration has any effect on circulating IGF-1, insulin, and IGFBP3 levels, two weeks after the start of metformin administration and six weeks after discontinuing metformin (week 20)
Time frame: 2 years
Determine if daily metformin administration has any effect on skeletalmuscle mitochondrial function using phosphorous-31 magnetic resonance spectroscopy (31P-MRS) baseline and eight weeks after the start of metformin.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2020.
- Background: PubMed 5360287Li FP, Fraumeni JF Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 1969 Oct;71(4):747-52. doi: 10.7326/0003-4819-71-4-747. No abstract available.
- Background: PubMed 3409256Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, Miller RW. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988 Sep 15;48(18):5358-62.
- Background: PubMed 21601526Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011 Jun;12(6):559-67. doi: 10.1016/S1470-2045(11)70119-X. Epub 2011 May 19.
- Derived from this study: PubMed 27869650Wang PY, Li J, Walcott FL, Kang JG, Starost MF, Talagala SL, Zhuang J, Park JH, Huffstutler RD, Bryla CM, Mai PL, Pollak M, Annunziata CM, Savage SA, Fojo AT, Hwang PM. Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome. J Clin Invest. 2017 Jan 3;127(1):132-136. doi: 10.1172/JCI88668. Epub 2016 Nov 21.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christina M Annunziata, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin in people with Li-Fraumeni Syndrome, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the tolerability of metformin in patients with LFS caused by germline TP53 mutations (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01981525, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2020.