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

NCT00334542 | Completed Phase 2 Results DMC

• 7 other identifiers: J0485P50CA088843P30CA006973JHOC-J0485SKCCC-J0485CDR0000477214NA_00041153
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (2)

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

  Baseline and week 24

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

  Baseline and week 24

Secondary Outcomes (2)

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

  Change from Baseline to week 24

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

  Baseline and week 24

Study Arms (1)

Simvastatin

EXPERIMENTAL

Simvastatin 40 mg for 24-28 weeks

Drug: simvastatin

Interventions

simvastatin DRUG

24-28 weeks of simvastatin

Also known as: Zocor

Simvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

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

Boston, Massachusetts, 02115-6084, United States

Location

Related Publications (2)

• 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.

  PMID: 15231653 BACKGROUND

• 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.

  PMID: 22076478 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Vered Stearns
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

vstearn1@jhmi.edu

4432876489

Study Officials

• Vered Stearns, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2006
• First Posted: June 8, 2006
• Study Start: March 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: November 1, 2011
• Last Updated: April 3, 2019
• Results First Posted: June 25, 2013

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)