Simvastatin and Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ or Invasive Breast Cancer

Official Title: “A Trial Assessing the Effect of Simvastatin on the Pharmacokinetics of Anastrozole”

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of simvastatin and anastrozole may stop cancer from forming, growing, or coming back in patients with invasive breast cancer, ductal carcinoma in situ, or a high risk of breast cancer.

PURPOSE: This phase II trial is studying how well giving simvastatin together with anastrozole works in treating postmenopausal women with invasive breast cancer, ductal carcinoma in situ, or a high risk of breast cancer.

OBJECTIVES:

Primary - Assess the effects of concurrent anastrozole and simvastatin on anastrozole's steady-state concentration in postmenopausal women with history of invasive breast cancer or ductal carcinoma in situ or at high risk for developing breast cancer.

Secondary - Study the effect of concurrent simvastatin and anastrozole on estrogen suppression in these patients.

OUTLINE: This is a pilot study.

Patients continue to receive oral anastrozole once daily (as prior to study entry). They also receive oral simvastatin once daily for 14-18 days in the absence of unacceptable toxicity or diagnosis of new or recurrent breast cancer.

Patients undergo blood sample collection at baseline and after study therapy for analysis of anastrozole and hormone (estradiol and estrogen) concentrations.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: anastrozole
  • 1 milligram tablet PO QD for 14 days
• Drug: simvastatin
  • 40 milligram tablet PO QD for 14 days
• Other: pharmacological study
  • laboratory analysis
• Procedure: adjuvant therapy
  • laboratory analysis

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Anastrozole and Simvastatin

Primary Measures

• Percentage change in blood concentrations of anastrozole at 14 days
  • Time Frame: 14 days
    Safety Issue?: No

Secondary Measures

• Percent reduction of serum estradiol levels at 14 days
  • Time Frame: 14 days
    Safety Issue?: No

DISEASE CHARACTERISTICS:

• Meets any of the following criteria:
• History of invasive breast cancer
• History of ductal carcinoma in situ
• At high risk for breast cancer, defined as being on anastrozole for chemoprevention of breast cancer
• Receiving anastrozole for ≥ 30 days as adjuvant breast cancer treatment or for prevention of breast cancer
• No active breast cancer with known metastatic involvement
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal
• ECOG performance status 0-2
• AST and ALT ≤ 3 times upper limit of normal
• Creatinine clearance ≥ 30 mL/min
• No active liver disease
• No prior hypersensitivity to any HMG-CoA reductase inhibitor or any of its components
• No daily alcohol use of > 3 standard drinks/day
• A standard drink is defined as 10 g of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine, or 30 mL of liquor

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No cholesterol-lowering drug, including a statin, within the past 3 months
• No selective estrogen receptor modulator (SERM) within the past 3 months
• No other hormone therapy within the past 3 months
• No prior estrogen and/or progesterone hormone replacement therapy that lasted for ≥ 5 years
• Vaginal estrogen preparations allowed
• No other concurrent statin or cholesterol-lowering drug
• No other concurrent SERM
• No other concurrent hormone therapy
• No other concurrent investigational drugs
• No concurrent CYP3A4 inhibitors, including itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, or cyclosporine
• No concurrent chemotherapy or biological agents
• No concurrent daily grapefruit juice > 8 oz/day
• No other concurrent anticancer agents or therapies

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sidney Kimmel Comprehensive Cancer Center Other

Overall Clinical Trial Officials and Contacts

Vered Stearns, MD Principal Investigator Sidney Kimmel Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00354640

Study ID Number: J05100, CDR0000485361

ClinicalTrials.gov Identifier: NCT00354640

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database