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

NCT ID: NCT00245024

Last Updated: 2013-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2010-01-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Interventions

sulindac

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Arizona

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Arizona Cancer Center at University of Arizona Health Science Center

Principal Investigators

Patricia Thompson, PhD

Role: STUDY_CHAIR

University of Arizona

Locations

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Countries

United States

References

Thompson PA, Huang C, Yang J, Wertheim BC, Roe D, Zhang X, Ding J, Chalasani P, Preece C, Martinez J, Chow HS, Stopeck AT. Sulindac, a Nonselective NSAID, Reduces Breast Density in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors. Clin Cancer Res. 2021 Oct 15;27(20):5660-5668. doi: 10.1158/1078-0432.CCR-21-0732. Epub 2021 Jun 10.

Reference Type: DERIVED

PMID: 34112707 (View on PubMed)

Other Identifiers

P30CA023074

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UARIZ-UAZ04-2-02

Identifier Type: -

Identifier Source: secondary_id

UARIZ-HSC-0553

Identifier Type: -

Identifier Source: secondary_id

CDR0000447144

Identifier Type: -

Identifier Source: org_study_id