Clinical trial NCT01980823: Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
Official title: Pre-Surgical "Window of Opportunity" Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Breast Cancer
Breast Tumors
Cancer of Breast
Keywords: Breast Cancer
Metformin
Atorvastatin
Ki-67
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2013-11-11
Enrollment: 23
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in tissue levels of the proliferation marker Ki-67
timeFrame: Baseline, 2 weeks after start of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Cancer Center
state: New York
Study officials:
affiliation: Columbia University
name: Katherine Crew, MD
role: PRINCIPAL_INVESTIGATOR
References: