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

NCT ID: NCT01980823

Last Updated: 2023-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2022-12-31

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.

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.

Conditions

Breast Cancer; Breast Tumors; Cancer of Breast

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin-Atorvastatin combination

Patients will receive metformin and atorvastatin for approximately 2 weeks prior to breast surgery.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: 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.

Atorvastatin

Intervention Type: 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.

Breast surgery

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

Glucophage; Lipitor; No other name

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Katherine D. Crew

Associate Professor of Medicine and Epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katherine Crew, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center - Herbert Irving Cancer Center

New York, New York, United States

Countries

United States

Related Links

https://cancer.columbia.edu/

Herbert Irving Comprehensive Cancer Center (HICCC) Clinical Trials Page

Other Identifiers

AAAM2306

Identifier Type: -

Identifier Source: org_study_id