Sulindac in Preventing Breast Cancer in Women at High Risk for Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of sulindac may prevent breast cancer. PURPOSE: This randomized phase I trial is studying the effects of sulindac, to prevent breast cancer, in women at high risk for breast cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the partitioning of sulindac and its metabolites in women at high risk for breast cancer by measuring drug and metabolite levels in nipple aspirate fluid (NAF) after 6 weeks of therapy. Secondary Determine prostaglandin levels in the NAF of patients treated with this drug. Determine if NAG-1 levels are induced in the NAF of patients treated with this drug. Determine if C-reactive protein levels are reduced in the NAF of patients treated with this drug. Determine if NAG-1 levels and/or karyometric features in ductal epithelial cells are modulated in patients treated with this drug. OUTLINE: This is a randomized, open-label study. Patients undergo nipple aspirate fluid (NAF) collection. Patients are then randomized to 1 of 2 treatment arms. Arm I: Patients receive oral sulindac once daily. Arm II: Patients receive oral sulindac twice daily. In both arms, treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. All patients then undergo a second NAF collection. After completion of study treatment, patients are followed at 2 weeks. PROJECTED ACCRUAL: A total of 30 patients (15 per treatment arm) will be accrued for this study.

Official Title
-----------------
Phase IB Sulindac Study for Women at High Risk for Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: sulindac
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Meets 1 of the following criteria: Gail assessment score > 1.7% risk for 5 years History of lobular carcinoma in situ (pathology report required) History of ductal carcinoma in situ (DCIS) (pathology report required) History of breast cancer in ≥ 1 first-degree relative or history of BRCA1 or BRCA2 positivity not treated with oophorectomy or mastectomy (test report required) History of breast cancer in ≥ 2 second-degree relatives Any family history of breast cancer diagnosed prior to age 50 Personal history of breast cancer (invasive or DCIS) with 1 breast intact Nipple aspirate fluid production ≥ 5 microliters Negative mammogram for breast cancer within the past 10 months Any suspicious breast masses must be examined by a clinical professional Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Sex Female Menopausal status Pre- or postmenopausal Performance status Karnofsky 80-100% Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No history of bleeding or clotting disorder Hepatic Bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2.0 times upper limit of normal No indication of abnormal liver function Renal Creatinine normal Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Gastrointestinal No frequent, chronic, or moderate/severe gastric complaint No upper gastrointestinal problems (e.g., symptoms of heartburn, dyspepsia, or abdominal pain) requiring prescription or nonprescription medical remedies more than once per week (on average) No history of peptic ulcer or occult or gross intestinal bleeding Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reaction (e.g., urticaria, asthma, rhinitis) or gastric intolerance attributed to compounds of similar chemical or biological composition to sulindac No history of allergy attributed to lidocaine, EMLA® cream, or xylocaine No concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No more than 2-3 servings of alcohol per week during study participation PRIOR CONCURRENT THERAPY: Chemotherapy More than 6 months since prior chemotherapy for breast cancer (invasive or DCIS) Endocrine therapy More than 6 months since prior hormonal therapy for breast cancer (invasive or DCIS) No concurrent hormone-suppressing agents (e.g., tamoxifen or anastrozole) No concurrent selective estrogen-receptor modulators No concurrent aromatase inhibitors Radiotherapy More than 6 months since prior radiotherapy for breast cancer (invasive or DCIS) Surgery See Disease Characteristics No prior breast duct-disrupting surgery (e.g., mastectomy) that would preclude ductoscopy Other More than 3 months since prior warfarin or other systemic anticoagulant More than 4-6 weeks since prior nonsteroidal anti-inflammatory drugs No concurrent phenytoin or sulfonamides No concurrent warfarin or other systemic anticoagulant No other concurrent nonsteroidal anti-inflammatory drugs (including low-dose aspirin) No concurrent large doses of supplements, vitamins (> regular daily multivitamin) and/or herbal medicines (e.g., echinacea, ginkgo biloba, Hypericum perforatum [St. John's wort], or herbal tea) No other concurrent investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: sulindac|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sulindac and sulindac metabolite levels in nipple aspirate fluid (NAF) after 6 weeks of treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostaglandin (PGE2) levels in NAF before and after 6 weeks of treatment |  |  | 
| NAG-1 induction and C-reactive protein (CRP) reduction before and after 6 weeks of treatment |  |  | 
| Magnitude of change and dose response of PGE2, NAG-1, and CRP in NAF before and after 6 weeks of treatment |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, ductal breast carcinoma in situ, lobular breast carcinoma in situ, breast cancer in situ