Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-00044 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2017-073 | Other Identifier | Wayne State University/Karmanos Cancer Institute | |
| P30CA022453 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (simvastatin) | Experimental | Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Laboratory Biomarker Analysis | Other | Correlative studies |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry | Differences in % positive cells pre and post treatment along with 95% confidence interval | Baseline up to 4 weeks |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline up to 4 weeks |
| Cleaved Caspase-3 (CC3) as a Marker of Apoptosis |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Michael Simon | Barbara Ann Karmanos Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33587350 | Derived | Asari K, Sun WT, Kok ZH, Lam YH, Ng BL, Saunders V, White DL, Chuah C, Xiang W. Simvastatin enhances the efficacy of nilotinib in chronic myeloid leukaemia by post-translational modification and drug transporter modulation. Anticancer Drugs. 2021 Jun 1;32(5):526-536. doi: 10.1097/CAD.0000000000001028. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Simvastatin) | Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Simvastatin: Given PO |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 4, 2020 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Simvastatin |
| Drug |
Given PO |
|
|
The difference in (percentage of cells cleaved caspase-3 (CC3)+) from pre-treatment to post-treatment
| Baseline up to 4 weeks |
| C-reactive Protein (CRP) as a Marker of Inflammation | c-reactive protein (CRP) as a marker of inflammation. | 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 | Baseline up to 4 weeks |
| Changes in p27 Cytoplasmic Intensity | the difference in (p27 cytoplasmic intensity) from pre-treatment to post-treatment | 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; | Baseline up to 4 weeks |
| COMPLETED |
|
| NOT COMPLETED |
|
|
All evaluable patients, including those recevied >80% doses
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Simvastatin) | Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Simvastatin: Given PO |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Number | participants |
| |||||||||||||||||||||||
| Estrogen Receptor Status | Count of Participants | Participants |
| |||||||||||||||||||||||
| Progesterone Receptor Status | Count of Participants | Participants |
| |||||||||||||||||||||||
| HER2 Status | Count of Participants | Participants |
| |||||||||||||||||||||||
| Tumor Stage | Stage 0: In Situ; the cancer is limited to the inside of the milk duct and is non-invasive (does not invade nearby tissues). Stage I: Invasive; Primary Tumor < 20mm; No lymph nodes affected; No metastasis Stage II: Invasive: Primary Tumor 20-50 mm; No lymph node involvement OR lymph node involvement of < 4 lymph nodes in the same side of the breast; No metastasis | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry | Differences in % positive cells pre and post treatment along with 95% confidence interval | one patient did not have pre and post measures | Posted | Mean | 95% Confidence Interval | percentage of cells expressing Ki67 | Baseline up to 4 weeks |
|
|
| |||||||||||||||||||||||||
| Other Pre-specified | 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 | Posted | Mean | 95% Confidence Interval | percentage of cells 'biomarker' positive | Baseline up to 4 weeks |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | 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 | Posted | Mean | 95% Confidence Interval | percentage of cells expressing CC3 | Baseline up to 4 weeks |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | C-reactive Protein (CRP) as a Marker of Inflammation | c-reactive protein (CRP) as a marker of inflammation. | This biomarker was not measured. | Posted | Baseline up to 4 weeks |
|
| |||||||||||||||||||||||||||||
| Other Pre-specified | Change in (% Intracellular p27 +) From Pre-treatment to Post-treatment | the difference in (% intracellular p27 +) from pre-treatment to post-treatment | Posted | Mean | 95% Confidence Interval | percentage of intracellular p27 + | Baseline up to 4 weeks |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | Changes in p27 Cytoplasmic Intensity | the difference in (p27 cytoplasmic intensity) from pre-treatment to post-treatment | Posted | Mean | 95% Confidence Interval | arbitrary units | Baseline up to 4 weeks |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | Changes in Cyclin D1 | the difference in % cyclin D1+ stained out of total cells from pre-treatment to post-treatment; | all 16 evaluable participants, except that one patient's sample did not yield cyclin D1 measurement. | Posted | Mean | 95% Confidence Interval | percentage of total cells cyclin + | Baseline up to 4 weeks |
|
|
from enrollment up to 18 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Simvastatin) | Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Simvastatin: Given PO | 0 | 17 | 0 | 17 | 2 | 17 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Bladder infection | Infections and infestations | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Simon,MD | Karmanos Cancer Institute | 313. 576-8727 | simonm@karmanos.org |
| Jun 14, 2022 |
| Prot_SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Unknown |
|
| Title |
|---|
| Measurements |
|---|
|
| Stage II: Primary Tumor 20-50 mm; 0-<4 lymph nodes in the same side of the breast; No metastasis |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|