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AzTrials

Breast CancerPhase 2NCT00334542

Simvastatin in Preventing a New Breast Cancer in Women at High Risk for a New Breast Cancer

A Phase 2 study testing simvastatin in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of simvastatin may keep cancer from coming back in women who are at high risk for a new breast cancer after undergoing surgery for ductal carcinoma in situ or stage I, stage II, or stage III breast… 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?
simvastatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesUnited States
Study dates
Mar 2006to Nov 2011
Phase
Phase 2
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

DISEASE CHARACTERISTICS:

  • History of histologically confirmed breast cancer, meeting 1 of the following staging criteria:
  • Ductal carcinoma in situ
  • Stage I-III invasive breast cancer
  • At least 3 months since completion of all intended local and systemic therapy, including mastectomy or lumpectomy with or without radiotherapy, adjuvant chemotherapy, and/or endocrine therapy
  • May have declined recommended treatment provided all treatment intended/agreed upon by the patient and treating physician was completed ≥ 3 months ago
  • At least 1 healthy intact breast
  • No prior radiotherapy or mastectomy
  • Prior biopsies allowed
  • Any hormone-receptor status

PATIENT CHARACTERISTICS:

  • Female
  • Pre- or post-menopausal
  • ECOG performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective nonhormonal contraception
  • No active liver disease
  • AST and ALT ≤ 3 times upper limit of normal
  • Creatinine clearance ≥ 30 mL/min
  • No prior hypersensitivity to any 3-hydroxyl-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitor or any of its components
  • No other concurrent infectious, inflammatory, or autoimmune diseases (at the discretion of principal investigator)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No daily alcohol use > 3 standard drinks per day
  • Standard drink defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine, or 30 mL of liquor
  • No selective estrogen receptor modulator or aromatase inhibitor within the past 3 months
  • No hormone replacement therapy (HRT) within the past 3 months
  • No prior estrogen and/or progesterone HRT ≥ 5 years in duration
  • Vaginal estrogen preparations allowed
  • No concurrent HRT
  • No other cholesterol-lowering drug, including a statin, within the past 3 months
  • No concurrent itraconazole, ketoconazole, nefazodone, cyclosporine, HIV protease inhibitors, clarithromycin, erythromycin, mibefradil, carbamazepine, bosentan, chaparral, amiodarone, or verapamil
  • No concurrent daily grapefruit juice consumption > 8 ounces per day
  • No other concurrent agents or therapies intended to treat or prevent in situ or invasive breast cancer

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

    Boston, Massachusetts, 02115-6084

Other trials in United States

About this study

Official title: A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of simvastatin may keep cancer from coming back in women who are at high risk for a new breast cancer after undergoing surgery for ductal carcinoma in situ or stage I, stage II, or stage III breast cancer.

PURPOSE: This phase II trial is studying how well simvastatin works in preventing a new breast cancer in women at high risk for a new breast cancer after undergoing surgery for ductal carcinoma in situ or stage I, stage II, or stage III breast cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Describe changes from baseline in a panel of biomarkers (high-sensitivity C-reactive protein [hsCRP], lipid profile, circulating estrogens, and contralateral breast density) in women at high risk of developing new breast cancer who have undergone surgical resection for history of ductal carcinoma in situ or stage I-III invasive breast cancer treated with simvastatin.

Secondary

  • Correlate changes in the panel of biomarkers with wild-type versus polymorphic 3-hydroxyl-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in women treated with simvastatin.

Tertiary

  • Evaluate methylation status across a panel of genes that are known to be frequently and specifically hypermethylated in ductal carcinoma in situ (DCIS) and invasive breast cancer (estrogen receptor [ER]-α and ER-β, cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) and correlate change in cumulative methylation with change in hsCRP, lipid profile, contralateral breast density, estrogen concentrations, and pharmacogenetics.
  • Measure changes in the phosphoinositide 3'-kinase (PI3K)/protein kinase B (Akt) signaling pathway (Akt and p-Akt) before and after treatment with simvastatin.

OUTLINE: This is a multicenter study. Patients are stratified according to menopausal status (pre- vs post-menopausal).

Patients receive oral simvastatin once daily for 24-28 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and at the end of study treatment for pharmacogenetic and biomarker correlative studies. Patients undergo mammography and measurement of breast density of the contralateral breast at baseline and at the end of study treatment.

Quality of life is assessed at baseline and at the end of study treatment.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Conditions
Breast Cancer
Being tested
simvastatin
Keywords
breast cancer, ductal breast carcinoma in situ, breast cancer in situ, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Medical subject headings
Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • simvastatinDrug

    Also called Zocor

    24-28 weeks of simvastatin

Study groups in NCT00334542
Study groupRoleWhat they receive
SimvastatinExperimentalSimvastatin 40 mg for 24-28 weeks
Receives: Drug: simvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline

    Measured: Baseline and week 24

  2. Change in a Panel of Biomarkers (Contralateral Breast Density) From Baseline

    Measured: Baseline and week 24

Secondary outcomes (2)

  1. Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation

    Median change in gene promotor methylation (%M) in the contralateral breast of women with breast cancer after six months of therapy

    Measured: Change from Baseline to week 24

  2. Prevalence of Akt and p-Akt Activation by Contralateral Core Breast Biopsies

    Measured: Baseline and week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionJun 2009
  4. Study completionNov 2011

Resources

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 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00334542
Sponsor's protocol ID
J0485
Other IDs
P50CA088843, P30CA006973, JHOC-J0485, SKCCC-J0485, CDR0000477214, NA_00041153
Status last verified
Mar 2019
First submitted
7 Jun 2006
Last updated
3 Apr 2019
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A, Garrett E, Argani P, Sukumar S. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 2004 Jul 1;64(13):4442-52. doi: 10.1158/0008-5472.CAN-03-3341.

    PubMed 15231653

  • Higgins MJ, Prowell TM, Blackford AL, Byrne C, Khouri NF, Slater SA, Jeter SC, Armstrong DK, Davidson NE, Emens LA, Fetting JH, Powers PP, Wolff AC, Green H, Thibert JN, Rae JM, Folkerd E, Dowsett M, Blumenthal RS, Garber JE, Stearns V. A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer. Breast Cancer Res Treat. 2012 Feb;131(3):915-24. doi: 10.1007/s10549-011-1858-7. Epub 2011 Nov 11.

    PubMed 22076478

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing simvastatin in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 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?

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 3 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2013). 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 a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline (time frame: Baseline and week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00334542, which also lists 2 linked publications.

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 3 Apr 2019.

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