Metformin Hydrochloride in Treating Women With Stage I or Stage II Breast Cancer That Can Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT00984490|
Recruitment Status : Terminated (slow accrual)
First Posted : September 25, 2009
Results First Posted : July 13, 2012
Last Update Posted : July 13, 2012
RATIONALE: Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying how well metformin hydrochloride works in treating women with stage I or stage II breast cancer that can be removed by surgery.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: metformin hydrochloride Other: laboratory biomarker analysis||Not Applicable|
- To determine the in situ effects of metformin hydrochloride on proliferation (Ki67) and apoptosis (caspase-3) in women with operable stage I or II breast cancer.
- To determine the in situ biologic effect of metformin hydrochloride on the AMP kinase, MTOR/PI3K, and IGF pathways in breast cancer (tissue S6K and phospho S6K, p53, p63, and p73 levels as well as p53 [(Ser-15), if wild-type p53 is present], p63 [Ser-66/68, Ser-301, and Ser-361], and p73 [Y-99] phosphorylation, PTEN [clone 6H2.1], phospho-Akt [S473], insulin receptor substrate 1 and 2 [IRS-1 and IRS-2], and LKB1).
- To determine if molecular classification (basal-type vs luminal A vs luminal B) and the established p63 and p73 RNA microarray gene signatures correlate with the metformin hydrochloride-induced effects on proliferation (Ki67), apoptosis (caspase-3) and the selected biomarkers (listed above) in breast cancer.
- To collect and analyze pre- and post-treatment peripheral blood specimens for serum glucose and insulin levels, as well as circulating IGF-1 and IGF binding protein 3 (IGFBP3).
OUTLINE: Patients receive oral metformin hydrochloride twice daily for 7-21 days. Approximately 24-36 hours after the last dose of metformin hydrochloride, patients undergo surgical resection (total mastectomy or segmental resection with lymph node evaluation) of tumor.
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pre-Surgical Trial of Metformin in Patients With Operable Breast Cancer|
|Study Start Date :||September 2009|
|Actual Primary Completion Date :||July 2010|
|Actual Study Completion Date :||July 2011|
Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery
Drug: metformin hydrochloride
Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgeryOther: laboratory biomarker analysis
Blood and tissue collection to determine the in situ biologic effect of metformin
- Change in Ki67 Levels Before and After Treatment [ Time Frame: baseline and between 8-23 days ]Change in Ki67 levels in pre-treatment, pre-surgery and post-treatment, surgically excised breast tissue. Measured by percentage of positive-staining nuclei with a minimum of 0% to a maximum of 100%. A mean score is determined.
- Changes in Circulating Insulin-like Growth Factor 1 (IGF-1) and IGF Binding Protein 3 (IGFBP-3) [ Time Frame: baseline and 23 days ]Effect of study drug on circulating IGF-1 and IGFBP-3 as measured in ng/mL in peripheral blood samples taken pre-treatment and post-treatment with metformin
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00984490
|United States, Georgia|
|Emory University Hospital|
|Atlanta, Georgia, United States, 30322|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center - Cool Springs|
|Nashville, Tennessee, United States, 37064|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Principal Investigator:||Ingrid Mayer, M.D.||Vanderbilt-Ingram Cancer Center|