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NCT Number: NCT01980823

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Breast Tumors Cancer of Breast Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

21 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Early Phase 1

Primary location

Columbia University Medical Center - Herbert Irving Cancer Center

New York, 10032, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

metformin

Drug

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 names: Glucophage

atorvastatin

Drug

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 names: Lipitor

Breast surgery

Procedure

(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 names: No other name

Primary outcomes

  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.

Sponsors and collaborators

Lead sponsor

Columbia University

Other

Registry information

Official study title

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

Important dates

Study start
2013
Primary completion
2018
Study completion
2022
First posted
Nov 11, 2013
Registry last updated
Aug 30, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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