A Phase 2 interventional study of Laboratory Biomarker Analysis and Simvastatin in Invasive Breast Carcinoma, Stage I Breast Cancer AJCC v7 and Stage IA Breast Cancer AJCC v7, sponsored by Michael Simon. Completed at 1 site in United States. Open to female participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2023-08-01.
Sponsored by Michael Simon · Phase 2, Interventional, and Treatment
The purpose of this pilot phase II trial is to identify the molecular and genetic mechanisms by which statins influence breast cancer cell proliferation. Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and reduce the aggressiveness of breast cancer cells.
PRIMARY OBJECTIVES:
I. Evaluate the relationship between short-term use of oral simvastatin on change in expression of Ki-67 as a candidate biomarker of breast tumor proliferation among women with clinical stage 1 or 2- primary invasive breast cancer.
II. Evaluate the relationship between short-term use of oral simvastatin on changes in other candidate predictive markers of breast tumor proliferation (cyclin D1 and P27), changes in a marker of apoptosis (cleaved caspase-3 [CC3]), changes in a marker of inflammation (c-reactive protein [CRP]) and as novel additional biomarkers changes in the composition of the plasma membrane (lipid rafts) and changes in activation of signaling markers (phosphorylation [p]Akt, pMAPK, pEGFR, PHER2).
III. To conduct exploratory analyses comparing the effect of statins on breast tumor proliferation and apoptosis in groups defined by tumor expression of hydroxymethylglutaryl co-enzyme A (CoA) reductase (HMG-CoA), estrogen receptor (ER)/progesterone receptor (PR) status, HER2neu, and tumor grade.
OUTLINE:
Patients receive simvastatin orally (PO) daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 24 is below the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →This is the only study on the registry with Michael Simon as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis · Drug: Simvastatin
Correlative studies
Given PO
Also known as: MK 733, Synvinolin, Zocor
Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry
Differences in % positive cells pre and post treatment along with 95% confidence interval
Time frame: Baseline up to 4 weeks
Change in Percentage of Cells P27+ From Pre-treatment to Post-treatment
The difference in percentage of cells P27+ from pre-treatment to post-treatment
Time frame: Baseline up to 4 weeks
Cleaved Caspase-3 (CC3) as a Marker of Apoptosis
The difference in (percentage of cells cleaved caspase-3 (CC3)+) from pre-treatment to post-treatment
Time frame: Baseline up to 4 weeks
C-reactive Protein (CRP) as a Marker of Inflammation
c-reactive protein (CRP) as a marker of inflammation.
Time frame: Baseline up to 4 weeks
Change in (% Intracellular p27 +) From Pre-treatment to Post-treatment
the difference in (% intracellular p27 +) from pre-treatment to post-treatment
Time frame: Baseline up to 4 weeks
Changes in p27 Cytoplasmic Intensity
the difference in (p27 cytoplasmic intensity) from pre-treatment to post-treatment
Time frame: Baseline up to 4 weeks
Changes in Cyclin D1
the difference in % cyclin D1+ stained out of total cells from pre-treatment to post-treatment;
Time frame: Baseline up to 4 weeks
| Milestone | Treatment (Simvastatin) |
|---|---|
| Started | 24 |
| Completed | 17 |
| Not completed | 7 |
| Withdrew: Did not receive treatment | 6 |
| Withdrew: Received < 80% doses | 1 |
Differences in % positive cells pre and post treatment along with 95% confidence interval
| percentage of cells expressing Ki67 | Treatment (Simvastatin) |
|---|---|
| Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry | 1.3 (-3.6 to 6.2) |
The difference in percentage of cells P27+ from pre-treatment to post-treatment
| percentage of cells 'biomarker' positive | Treatment (Simvastatin) |
|---|---|
| Change in Percentage of Cells P27+ From Pre-treatment to Post-treatment | -1.4 (-9.2 to 6.3) |
The difference in (percentage of cells cleaved caspase-3 (CC3)+) from pre-treatment to post-treatment
| percentage of cells expressing CC3 | Treatment (Simvastatin) |
|---|---|
| Cleaved Caspase-3 (CC3) as a Marker of Apoptosis | 5.4 (-1.3 to 12.1) |
c-reactive protein (CRP) as a marker of inflammation.
No measurements were reported for this outcome.
the difference in (% intracellular p27 +) from pre-treatment to post-treatment
| percentage of intracellular p27 + | Treatment (Simvastatin) |
|---|---|
| Change in (% Intracellular p27 +) From Pre-treatment to Post-treatment | 0.3 (-7.9 to 8.4) |
the difference in (p27 cytoplasmic intensity) from pre-treatment to post-treatment
| arbitrary units | Treatment (Simvastatin) |
|---|---|
| Changes in p27 Cytoplasmic Intensity | 1.8 (0.2 to 3.4) |
the difference in % cyclin D1+ stained out of total cells from pre-treatment to post-treatment;
| percentage of total cells cyclin + | Treatment (Simvastatin) |
|---|---|
| Changes in Cyclin D1 | 6.1 (-2.1 to 14.2) |
Collected over from enrollment up to 18 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Simvastatin) | 0/17 (0%) | 0/17 (0%) | 2/17 (11.8%) |
| Event | Treatment (Simvastatin) |
|---|---|
| Musculoskeletal and connective tissue disorder - Other, specifyMusculoskeletal and connective tissue disorders | 1/17 |
| Bladder infectionInfections and infestations | 1/17 |
All evaluable patients, including those recevied \>80% doses
| Age, Continuous(years) | Treatment (Simvastatin) |
|---|---|
| Median | 63 (48 to 73) |
| Sex: Female, Male(Participants) | Treatment (Simvastatin) |
|---|---|
| Female | 17 |
| Male | 0 |
| Race (NIH/OMB)(Participants) | Treatment (Simvastatin) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 6 |
| Region of Enrollment(participants) | Treatment (Simvastatin) |
|---|---|
| United States | 17 |
| Estrogen Receptor Status(Participants) | Treatment (Simvastatin) |
|---|---|
| Positive | 15 |
| Negative | 2 |
| Progesterone Receptor Status(Participants) | Treatment (Simvastatin) |
|---|---|
| Positive | 11 |
| Negative | 6 |
| HER2 Status(Participants) | Treatment (Simvastatin) |
|---|---|
| Positive | 0 |
| Negative | 12 |
| Unknown | 5 |
| Tumor Stage(Participants) | Treatment (Simvastatin) |
|---|---|
| Stage 0: limited to the inside of the milk duct; is non-invasive; does not invade nearby tissues. | 6 |
| Stage I: Invasive; Primary Tumor < 20mm; No lymph nodes affected; No metastasis. | 11 |
| Stage II: Primary Tumor 20-50 mm; 0-<4 lymph nodes in the same side of the breast; No metastasis | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2018 to primary completion in Oct 2021, 42 months.
Results were first posted in Aug 2023, 1 year 9 months after primary completion.
Of 1,070 non-industry phase 2 interventional studies under Breast Neoplasms, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 34 and three quarters within 87. This study's 42 months is below that.
Counting every sponsor, half of 1,302 studies reached it within 51 months; a quarter within 30 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Simvastatin