Breast CancerEarly Phase 1NCT01980823
Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
A Early Phase 1 study testing Metformin, Atorvastatin and Breast surgery in people with Breast Cancer and Breast Tumors, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older, women only
- Conditions the study is for
- Breast Cancer, Breast Tumors, Cancer of Breast
- What is being tested?
- Metformin, Atorvastatin and Breast surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center - Herbert Irving Cancer Center
New York, New York, 10032
About this study
Official title: 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.
Read the 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
- Being tested
- Metformin, Atorvastatin, Breast surgery
- Keywords
- Breast Cancer, Metformin, Atorvastatin, Ki-67
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
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.
AtorvastatinDrug
Also called Lipitor
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 surgeryProcedure or surgery
Also called No other name
(Non-experimental) Female subjects with histologically-confirmed operable invasive breast cancer or DCIS will undergo core needle biopsy with a plan of surgical excision.
| Study group | Role | What they receive |
|---|---|---|
| Metformin-Atorvastatin combination | Experimental | Patients will receive metformin and atorvastatin for approximately 2 weeks prior to breast surgery. Receives: Drug: Metformin; Drug: Atorvastatin; Procedure: Breast surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in tissue levels of the proliferation marker Ki-67
Tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells.
Measured: Baseline, 2 weeks after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2013 (estimated)
- Study startOct 2013
- Primary completion24 May 2018
- Study completionDec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katherine D. Crew, Columbia University
- Investigators
- Katherine Crew, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980823
- Sponsor's protocol ID
- AAAM2306
- Status last verified
- Aug 2023
- First submitted
- 5 Nov 2013
- Last updated
- 30 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-Surgical "Window of Opportunity" Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
- ClinicalTrials.gov ID
- NCT01980823
- Acronym / sponsor ID
- AAAM2306
- Conditions
- Breast Cancer, Breast Tumors, Cancer of Breast
- Keywords
- Breast Cancer, Metformin, Atorvastatin, Ki-67
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- 24 May 2018 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 11 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin-Atorvastatin combination | Experimental | Drug: Metformin, Drug: Atorvastatin, Procedure: Breast surgeryPatients will receive metformin and atorvastatin for approximately 2 weeks prior to breast surgery. |
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageMetformin 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. | Drug | Metformin-Atorvastatin combination |
| AtorvastatinAlso: LipitorAtorvastatin 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. | Drug | Metformin-Atorvastatin combination |
| Breast surgeryAlso: No other name(Non-experimental) Female subjects with histologically-confirmed operable invasive breast cancer or DCIS will undergo core needle biopsy with a plan of surgical excision. | Procedure or surgery | Metformin-Atorvastatin combination |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Herbert Irving Comprehensive Cancer Center (HICCC) Clinical Trials PageLink provided by the sponsor.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Crew, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Metformin, Atorvastatin and Breast surgery in people with Breast Cancer and Breast Tumors, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in tissue levels of the proliferation marker Ki-67 (time frame: Baseline, 2 weeks after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2023; AzTrials last refreshed its copy on 8 Nov 2026.