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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anastrozole
* Drug: simvastatin
* Other: pharmacological study
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anastrozole and Simvastatin<br>This is a pharmacological study for women on anastrozole as adjuvant therapy for breast cancer to receive concurrent simvastatin for up to 14 days. | Drug: anastrozole<br>* 1 milligram tablet PO QD for 14 days<br>* Other names: Arimidex;Drug: simvastatin<br>* 40 milligram tablet PO QD for 14 days<br>* Other names: Zocor;Other: pharmacological study<br>* laboratory analysis<br>Procedure: adjuvant therapy<br>* laboratory analysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Concentrations | The change in blood concentrations of anastrozole at baseline and 14 days was measured. | Baseline and 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Estradiol Levels | The change in serum concentrations of estradiol at baseline and 14 days was measured. | Baseline and 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, breast cancer in situ, ductal breast carcinoma in situ, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer