Metformin Hydrochloride in Treating Women With Stage I or Stage II Breast Cancer That Can Be Removed By Surgery

Not Applicable

Terminated

• Conditions: Breast Cancer
• Interventions: Drug: metformin hydrochloride; Other: laboratory biomarker analysis

• Registration Number: NCT00984490
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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 Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-24
• Study First Submitted QC: 2009-09-24
• Study First Posted: 2009-09-25
• Primary Completion: 2010-07
• Study Completion: 2011-07
• Results First Submitted: 2012-03-12
• Results First Submitted QC: 2012-06-07
• Results First Posted: 2012-07-13
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-09
• Last Update Posted: 2024-02-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metformin	laboratory biomarker analysis	Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery
Metformin	metformin hydrochloride	Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery

Primary Outcome Measures

Name	Time	Method
Change in Ki67 Levels Before and After Treatment	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.

Secondary Outcome Measures

Name	Time	Method
Changes in Circulating Insulin-like Growth Factor 1 (IGF-1) and IGF Binding Protein 3 (IGFBP-3)	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

Trial Locations

Locations (3)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Vanderbilt-Ingram Cancer Center - Cool Springs; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States