Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
Overview[ - collapse ][ - ]
| Purpose | 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. Metformin is a medication used to treat patients with diabetes. It has been shown to have anti-tumor properties in breast cancer. Atorvastatin is widely used for the treatment of elevated cholesterol and has also shown to have anti-tumor properties in breast cancer. Both have safely been used in patients without diabetes or elevated cholesterol. This study will assess the impact of combined metformin and atorvastatin on breast tumor tissue markers as well as blood levels, including cholesterol and insulin. Both medications will be given for two weeks prior to your scheduled breast surgery. |
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| Condition | Breast Cancer Breast Tumors Cancer of Breast |
| Intervention | Drug: Metformin, Atorvastatin combination |
| Phase | Phase 0 |
| Sponsor | Kevin Kalinsky |
| Responsible Party | Columbia University |
| ClinicalTrials.gov Identifier | NCT01980823 |
| First Received | November 5, 2013 |
| Last Updated | November 5, 2013 |
| Last verified | November 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | November 5, 2013 |
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| Last Updated Date | November 5, 2013 |
| Start Date | October 2013 |
| Estimated Primary Completion Date | October 2015 |
| Current Primary Outcome Measures | Natural log expression of Ki-67 staining of breast tumor cells [Time Frame: At least 2 weeks after start of treatment] [Designated as safety issue: No]Tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells, is reduced. |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer |
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| Official Title | Pre-Surgical "Window of Opportunity" Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer |
| 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. Metformin is a medication used to treat patients with diabetes. It has been shown to have anti-tumor properties in breast cancer. Atorvastatin is widely used for the treatment of elevated cholesterol and has also shown to have anti-tumor properties in breast cancer. Both have safely been used in patients without diabetes or elevated cholesterol. This study will assess the impact of combined metformin and atorvastatin on breast tumor tissue markers as well as blood levels, including cholesterol and insulin. Both medications will be given for two weeks prior to your scheduled breast surgery. |
| Detailed Description | Utilizing a pre-surgical model, we plan 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 for at least two weeks, in the interval between diagnostic breast biopsy and definitive breast surgery. In this pre-surgical trial, patients will receive metformin and atorvastatin at bedtime. Women with histologically-confirmed invasive breast cancer or DCIS will be recruited by the medical oncologist and will start the dual therapy at least two weeks prior to their scheduled surgery. The primary objective of this study is to evaluate changes in tissue levels of the proliferation marker Ki-67. These will be compared to a) historical control group of metformin treated patients and b) historical control matched by age, body mass index, and tumor stage who did not receive metformin or statin. Secondary endpoints include assessment of changes in protein expression of AMPK/mTOR signaling; modulation of apoptosis markers such as bax, bid, and various caspase levels; and changes in fasting serum markers of the insulin growth factor pathway such as insulin, glucose, and lipids. 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. |
| Study Type | Interventional |
| Study Phase | Phase 0 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
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| Intervention | Drug: Metformin, Atorvastatin combination |
| Study Arm (s) | Experimental: Metformin, Atorvastatin combination Participants will receive oral metformin and atorvastatin. |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 40 |
| Estimated Completion Date | October 2015 |
| Estimated Primary Completion Date | October 2015 |
| 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 CYP 3A4 inhibitors (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 |
| Gender | Female |
| Ages | 21 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Stephanie Aguilar 212-342-4591 sa3146@columbia.edu |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01980823 |
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| Other Study ID Numbers | AAAM2306 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Columbia University |
| Study Sponsor | Kevin Kalinsky |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Keven Kalinsky, MD Columbia University |
| Verification Date | November 2013 |
Locations[ + expand ][ + ]
| Columbia University Medical Center- Herbert Irving Cancer Center | Manhattan, New York, United States, 10032 Contact: Stephanie Aguilar | 212-342-4591 | sa3146@columbia.eduPrincipal Investigator: Kevin Kalinsky, MD Recruiting |
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