Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 21 - Any |
| Updated: | 3/31/2019 |
| Start Date: | October 2013 |
| End Date: | April 2020 |
| Contact: | Lisa Olmos, RN |
| Email: | cancerclinicaltrials@cumc.columbia.edu |
| Phone: | 212-342-5162 |
Pre-Surgical "Window of Opportunity" 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.
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.
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.
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.
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
We found this trial at
1
site
New York, New York 10032
Principal Investigator: Kevin Kalinsky, MD
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