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

Breast Cancer Clinical Trial

Official title:

Phase IB Sulindac Study for Women at High Risk for Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00245024
• Other study ID #: CDR0000447144
• Secondary ID: P30CA023074UARIZ
• Status: Completed
• Phase: Phase 1
• First received: October 25, 2005
• Last updated: May 1, 2013
• Start date: November 2005
• Est. completion date: January 2010

Study information

• Verified date: October 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2010
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• sulindac

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	University of Arizona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sulindac and sulindac metabolite levels in nipple aspirate fluid (NAF) after 6 weeks of treatment			No
Secondary	Prostaglandin (PGE2) levels in NAF before and after 6 weeks of treatment			No
Secondary	NAG-1 induction and C-reactive protein (CRP) reduction before and after 6 weeks of treatment			No
Secondary	Magnitude of change and dose response of PGE2, NAG-1, and CRP in NAF before and after 6 weeks of treatment			No