Breast CancerNCT00984490
Metformin Hydrochloride in Treating Women With Stage I or Stage II Breast Cancer That Can Be Removed By Surgery
A study testing metformin hydrochloride and laboratory biomarker analysis in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 3 sites in United States.
Trial summary
RATIONALE: Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying how well metformin hydrochloride works in treating women with stage I or stage II breast cancer that can be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- metformin hydrochloride and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2009to Jul 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must provide informed written consent
- Eastern Cooperative Oncology Group performance status 0-1.
- Clinical stage I, II or IIIA invasive mammary carcinoma, any estrogen receptors(ER), progesterone receptors (PR), or Human Epidermal Growth Factor Receptor (HER2/NEU) status
- Patients who have measurable residual tumor at the primary site Measurable disease: a mass that can be reproducibly measured by physical examination and/or ultrasound and is at least 1 cm in size by physical examination or ultra-sound measurement
- Patients who will undergo surgical treatment with either segmental resection or total mastectomy with lymph node evaluation
- Consultations: All patients should be evaluated by a surgeon prior to study entry.
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- Available core biopsies from the time of diagnosis. These may include sections paraffin-embedded material.
- Female subjects ≥18 years of age
- No prior chemotherapy for this primary breast cancer.
- Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer.
- Women may have been taking tamoxifen or raloxifene as a preventive agent prior to study entry but must have discontinued the drug for at least 21 days prior to study enrollment.
- Patients must have adequate hepatic and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
- Creatinine </= to 1.5X upper limits of normal
- Bilirubin, SGOT, SGPT < or = to 1.5X upper limits of normal
- Able to swallow and retain oral medication
Who cannot join
- Patients with locally advanced disease who are candidates and wish to undergo preoperative chemotherapy at the time of initial evaluation. Patients with operable locally advanced disease (stage IIIA) are eligible for participation.
- Locally recurrent breast cancer
- Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
- History of diabetes mellitus
- Pregnant or lactating women
- Metformin treatment within 30 days of study entry
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- Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded.
- History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- History of a medical condition leading to chronic hypoxemia and/or ischemia (congestive heart failure, emphysema or chronic lung disease requiring supplemental oxygen)
- Chronic metabolic acidosis (serum HCO3- < or = to 20 or requiring sodium bicarbonate supplementation)
- Concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or any other biologic therapy)
- Concurrent treatment with an investigational agent
- Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study drug.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University Hospital
Atlanta, Georgia, 30322
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: Pre-Surgical Trial of Metformin in Patients With Operable Breast Cancer
RATIONALE: Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying how well metformin hydrochloride works in treating women with stage I or stage II breast cancer that can be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To determine the in situ effects of metformin hydrochloride on proliferation (Ki67) and apoptosis (caspase-3) in women with operable stage I or II breast cancer.
Secondary
- To determine the in situ biologic effect of metformin hydrochloride on the AMP kinase, MTOR/PI3K, and IGF pathways in breast cancer (tissue S6K and phospho S6K, p53, p63, and p73 levels as well as p53 [(Ser-15), if wild-type p53 is present], p63 [Ser-66/68, Ser-301, and Ser-361], and p73 [Y-99] phosphorylation, PTEN [clone 6H2.1], phospho-Akt [S473], insulin receptor substrate 1 and 2 [IRS-1 and IRS-2], and LKB1).
- To determine if molecular classification (basal-type vs luminal A vs luminal B) and the established p63 and p73 RNA microarray gene signatures correlate with the metformin hydrochloride-induced effects on proliferation (Ki67), apoptosis (caspase-3) and the selected biomarkers (listed above) in breast cancer.
- To collect and analyze pre- and post-treatment peripheral blood specimens for serum glucose and insulin levels, as well as circulating IGF-1 and IGF binding protein 3 (IGFBP3).
OUTLINE: Patients receive oral metformin hydrochloride twice daily for 7-21 days. Approximately 24-36 hours after the last dose of metformin hydrochloride, patients undergo surgical resection (total mastectomy or segmental resection with lymph node evaluation) of tumor.
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
- Conditions
- Breast Cancer
- Being tested
- metformin hydrochloride, laboratory biomarker analysis
- Keywords
- stage I breast cancer, stage II breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin hydrochlorideDrug
Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery
laboratory biomarker analysisOther
Blood and tissue collection to determine the in situ biologic effect of metformin
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery Receives: Drug: metformin hydrochloride; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Ki67 Levels Before and After Treatment
Change in Ki67 levels in pre-treatment, pre-surgery and post-treatment, surgically excised breast tissue. Measured by percentage of positive-staining nuclei with a minimum of 0% to a maximum of 100%. A mean score is determined.
Measured: baseline and between 8-23 days
Secondary outcomes (1)
Changes in Circulating Insulin-like Growth Factor 1 (IGF-1) and IGF Binding Protein 3 (IGFBP-3)
Effect of study drug on circulating IGF-1 and IGFBP-3 as measured in ng/mL in peripheral blood samples taken pre-treatment and post-treatment with metformin
Measured: baseline and 23 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionJul 2010
- Study completionJul 2011
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Vandana Abramson, Vanderbilt-Ingram Cancer Center
- Investigators
- Ingrid Mayer, M.D., Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984490
- Sponsor's protocol ID
- VICC BRE 0942
- Other IDs
- P30CA068485, VU-VICC-BRE-0942
- Status last verified
- Jan 2024
- First submitted
- 24 Sep 2009
- Last updated
- 1 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-Surgical Trial of Metformin in Patients With Operable Breast Cancer
- ClinicalTrials.gov ID
- NCT00984490
- Acronym / sponsor ID
- VICC BRE 0942
- Conditions
- Breast Cancer
- Keywords
- stage I breast cancer, stage II breast cancer
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2009
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 25 Sep 2009 (estimated)
- Results
- Posted 13 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying how well metformin hydrochloride works in treating women with stage I or stage II breast cancer that can be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To determine the in situ effects of metformin hydrochloride on proliferation (Ki67) and apoptosis (caspase-3) in women with operable stage I or II breast cancer.
Secondary
- To determine the in situ biologic effect of metformin hydrochloride on the AMP kinase, MTOR/PI3K, and IGF pathways in breast cancer (tissue S6K and phospho S6K, p53, p63, and p73 levels as well as p53 [(Ser-15), if wild-type p53 is present], p63 [Ser-66/68, Ser-301, and Ser-361], and p73 [Y-99] phosphorylation, PTEN [clone 6H2.1], phospho-Akt [S473], insulin receptor substrate 1 and 2 [IRS-1 and IRS-2], and LKB1).
- To determine if molecular classification (basal-type vs luminal A vs luminal B) and the established p63 and p73 RNA microarray gene signatures correlate with the metformin hydrochloride-induced effects on proliferation (Ki67), apoptosis (caspase-3) and the selected biomarkers (listed above) in breast cancer.
- To collect and analyze pre- and post-treatment peripheral blood specimens for serum glucose and insulin levels, as well as circulating IGF-1 and IGF binding protein 3 (IGFBP3).
OUTLINE: Patients receive oral metformin hydrochloride twice daily for 7-21 days. Approximately 24-36 hours after the last dose of metformin hydrochloride, patients undergo surgical resection (total mastectomy or segmental resection with lymph node evaluation) of tumor.
Patients undergo blood and tissue sample collection periodically for biomarker analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: metformin hydrochloride, Other: laboratory biomarker analysisMetformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must provide informed written consent
- Eastern Cooperative Oncology Group performance status 0-1.
- Clinical stage I, II or IIIA invasive mammary carcinoma, any estrogen receptors(ER), progesterone receptors (PR), or Human Epidermal Growth Factor Receptor (HER2/NEU) status
- Patients who have measurable residual tumor at the primary site Measurable disease: a mass that can be reproducibly measured by physical examination and/or ultrasound and is at least 1 cm in size by physical examination or ultra-sound measurement
- Patients who will undergo surgical treatment with either segmental resection or total mastectomy with lymph node evaluation
Key exclusion criteria (15 listed)
- Patients with locally advanced disease who are candidates and wish to undergo preoperative chemotherapy at the time of initial evaluation. Patients with operable locally advanced disease (stage IIIA) are eligible for participation.
- Locally recurrent breast cancer
- Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
- History of diabetes mellitus
- Pregnant or lactating women
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 |
|---|---|---|
| metformin hydrochlorideMetformin: 850 mg orally (PO) twice daily (BID) for 7-21 days, discontinued 24-36 hrs prior to surgery | Drug | Metformin |
| laboratory biomarker analysisBlood and tissue collection to determine the in situ biologic effect of metformin | Other | Metformin |
Primary outcome
Change in Ki67 Levels Before and After Treatment
Time frame: baseline and between 8-23 days
Change in Ki67 levels in pre-treatment, pre-surgery and post-treatment, surgically excised breast tissue. Measured by percentage of positive-staining nuclei with a minimum of 0% to a maximum of 100%. A mean score is determined.
1 secondary outcome
Changes in Circulating Insulin-like Growth Factor 1 (IGF-1) and IGF Binding Protein 3 (IGFBP-3)
Time frame: baseline and 23 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ingrid Mayer, M.D. principal investigator
Vanderbilt-Ingram Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing metformin hydrochloride and laboratory biomarker analysis in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 3 sites 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 15 inclusion and 15 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: stopped early, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Ki67 Levels Before and After Treatment (time frame: baseline and between 8-23 days). 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 1 Feb 2024.