Breast Cancer
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGanastrozole
1 milligram tablet PO QD for 14 days
DRUGsimvastatin
40 milligram tablet PO QD for 14 days
OTHERpharmacological study
laboratory analysis
PROCEDUREadjuvant therapy
laboratory analysis
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Concentrations | Baseline and 14 days | The change in blood concentrations of anastrozole at baseline and 14 days was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Estradiol Levels | Baseline and 14 days | The change in serum concentrations of estradiol at baseline and 14 days was measured. |
Countries
United States
Participant flow
Recruitment details
Eleven women were enrolled from December 2006 to September 2008.
Pre-assignment details
Women were required to be taking anastrozole as adjuvant treatment for breast cancer.
Participants by arm
| Arm | Count |
|---|---|
| Anastrozole and Simvastatin adjuvant therapy : laboratory analysis
pharmacological study : laboratory analysis
simvastatin : 40 milligram tablet PO QD for 14 days
anastrozole : 1 milligram tablet PO QD for 14 days | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Anastrozole and Simvastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Change in Blood Concentrations
The change in blood concentrations of anastrozole at baseline and 14 days was measured.
Time frame: Baseline and 14 days
Population: Participants with blood samples for trough concentrations were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anastrozole and Simvastatin | Change in Blood Concentrations | Anastrozole concentration | 4.2 ng/ml |
| Anastrozole and Simvastatin | Change in Blood Concentrations | Hydroxyanastrozole concentration | -0.03 ng/ml |
Secondary
Change in Serum Estradiol Levels
The change in serum concentrations of estradiol at baseline and 14 days was measured.
Time frame: Baseline and 14 days
Population: Participants with blood samples for trough concentrations were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anastrozole and Simvastatin | Change in Serum Estradiol Levels | -3.0 pmol/l |