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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00334542
First received: June 7, 2006
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: simvastatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Change in a Panel of Biomarkers (Contralateral Breast Density) From Baseline [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
  • Prevalence of Akt and p-Akt Activation by Contralateral Core Breast Biopsies [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: March 2006
Study Completion Date: November 2011
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Simvastatin
Simvastatin 40 mg for 24-28 weeks
Drug: simvastatin
24-28 weeks of simvastatin
Other Name: Zocor

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334542

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115-6084
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Vered Stearns, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00334542     History of Changes
Other Study ID Numbers: JHOC-J0485, CDR0000477214, P50CA088843, P30CA006973, JHOC-J0485, SKCCC-J0485
Study First Received: June 7, 2006
Results First Received: March 18, 2013
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Simvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014