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Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01980823
Recruitment Status : Recruiting
First Posted : November 11, 2013
Last Update Posted : July 15, 2019
Information provided by (Responsible Party):
Kevin Kalinsky, Columbia University

Brief Summary:

The purpose of this study is to determine the effects of combining metformin and atorvastatin treatment in patients with newly diagnosed breast cancer during the interval between breast biopsy and surgery.

This study is designed to assess whether tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells, is reduced following approximately 2 weeks of treatment with the combination of metformin plus atorvastatin in patients with newly diagnosed breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Breast Tumors Cancer of Breast Drug: Metformin Drug: Atorvastatin Procedure: Breast surgery Early Phase 1

Detailed Description:

Breast cancer cells require energy homeostasis shifts with enhanced anabolism to enable rapid growth and continued proliferation. The main energy regulatory system in eukaryotes and breast cancer cells is the AMP-activated kinase (AMPK) pathway. AMPK is triggered by changes in the AMP/Adenosine triphosphate (ATP) ratio thus impacting energy reserves and requirements. AMPK pathway closely interacts with the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, affecting the downstream function of the master regulator mammalian target of rapamycin (mTOR). Activation of AMPK has been shown in vitro to result in inhibition of proliferation of various cancer cell lines.

Utilizing a pre-surgical model, the investigator plans to conduct a pilot study of 40 women with newly diagnosed invasive breast cancer or ductal carcinoma in-situ (DCIS) who will receive oral metformin and atorvastatin daily in the interval between diagnostic breast biopsy and definitive breast surgery.

The goal is to determine if dual combination treatment with metformin plus atorvastatin significantly impacts tumor-based markers, such as proliferation, and blood-based biomarkers.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pre-Surgical "Window of Opportunity" Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
Actual Study Start Date : October 2013
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Metformin-Atorvastatin combination
Patients will receive metformin and atorvastatin for approximately 2 weeks prior to breast surgery.
Drug: Metformin

Metformin is an oral diabetes medicine that helps control blood sugar levels.

Dosage/Frequency: 1500 mg per day: divided 500 mg in the morning and 1000 mg in the evening

Metformin is for people with type 2 diabetes. Metformin is sometimes used in combination with insulin or other medications, but it is not for treating type 1 diabetes.

Other Name: Glucophage

Drug: Atorvastatin

Atorvastatin is in a group of drugs called "statins." Atorvastatin reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL).

Dosage/Frequency: 80 mg once a day at bedtime

Atorvastatin is used to treat high cholesterol, and to lower the risk of stroke, heart attack, or other heart complications in people with type 2 diabetes, coronary heart disease, or other risk factors.

Other Name: Lipitor

Procedure: Breast surgery
(Non-experimental) Female subjects with histologically-confirmed operable invasive breast cancer or DCIS will undergo core needle biopsy with a plan of surgical excision.
Other Name: No other name

Primary Outcome Measures :
  1. Change in tissue levels of the proliferation marker Ki-67 [ Time Frame: Baseline, 2 weeks after start of treatment ]
    Tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female subjects with histologically-confirmed operable invasive breast cancer or DCIS, who undergo core needle biopsy followed by surgical excision at least 2 weeks after enrollment
  • ≥ 5 mm by imaging/pathology of core to ensure enough pre- and post-treatment tissue for analysis
  • Age ≥ 21 years. Breast cancer is uncommon in patients less than this age.
  • No prior chemotherapy, radiation therapy, or breast resection within 6 months of study entry
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • Signed informed consent

Exclusion Criteria:

  • Currently on medication for diabetes or hypercholesterolemia
  • Treatment with other investigational drugs within 6 months of study entry
  • Strong Cytochrome P450 3A4 (abbreviated CYP3A4) (e.g., clarithromycin, HIV protease inhibitors, and itraconazole), given potential interactions with atorvastatin
  • Renal impairment with a creatinine > 1.4 mg/dl
  • Hepatic impairment: Aspartate transaminase (AST)/(SGOT), Alanine Transaminase(ALT)/(SGPT) ≥ 2.5 x upper limit of normal range (ULN), OR Total bilirubin ≥ 1.5 x ULN (subjects with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN), OR Alkaline phosphatase > 2.5 x ULN

Information from the National Library of Medicine

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 identifier (NCT number): NCT01980823

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Contact: Lisa Olmos, RN 212-342-5162

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United States, New York
Columbia University Medical Center - Herbert Irving Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Kevin Kalinsky, MD   
Principal Investigator: Kevin Kalinsky, MD         
Sponsors and Collaborators
Columbia University
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Principal Investigator: Kevin Kalinsky, MD Columbia University

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Responsible Party: Kevin Kalinsky, Assistant Professor of Medicine, Columbia University Medical Center, Columbia University Identifier: NCT01980823    
Other Study ID Numbers: AAAM2306
First Posted: November 11, 2013    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Kevin Kalinsky, Columbia University:
Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors