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

NCT ID: NCT00334542

Last Updated: 2019-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2011-11-30

Brief 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 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Simvastatin

Simvastatin 40 mg for 24-28 weeks

Group Type: EXPERIMENTAL

simvastatin

Intervention Type: DRUG

24-28 weeks of simvastatin

Interventions

simvastatin

24-28 weeks of simvastatin

Intervention Type: DRUG

Other Intervention Names

Zocor

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vered Stearns, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

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

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15231653 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22076478 (View on PubMed)

Other Identifiers

P50CA088843

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0485

Identifier Type: OTHER

Identifier Source: secondary_id

SKCCC-J0485

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000477214

Identifier Type: REGISTRY

Identifier Source: secondary_id

NA_00041153

Identifier Type: OTHER

Identifier Source: secondary_id

J0485

Identifier Type: -

Identifier Source: org_study_id