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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Other: laboratory biomarker analysis

Drug: sulindac

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00245024

UARIZ-UAZ04-2-02

P30CA023074 (U.S. NIH Grant/Contract)

UARIZ-HSC-0553

CDR0000447144

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

Female

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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