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

Primary Purpose

Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sulindac
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer focused on measuring breast cancer, ductal breast carcinoma in situ, lobular breast carcinoma in situ, breast cancer in situ

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Arizona Cancer Center at University of Arizona Health Sciences Center

Outcomes

Primary Outcome Measures

Sulindac and sulindac metabolite levels in nipple aspirate fluid (NAF) after 6 weeks of treatment

Secondary Outcome Measures

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

Full Information

First Posted
October 25, 2005
Last Updated
May 1, 2013
Sponsor
National Cancer Institute (NCI)
Collaborators
University of Arizona
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1. Study Identification

Unique Protocol Identification Number
NCT00245024
Brief Title
Sulindac in Preventing Breast Cancer in Women at High Risk for Breast Cancer
Official Title
Phase IB Sulindac Study for Women at High Risk for Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
January 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)
Collaborators
University of Arizona

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
breast cancer, ductal breast carcinoma in situ, lobular breast carcinoma in situ, breast cancer in situ

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
sulindac
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Primary Outcome Measure Information:
Title
Sulindac and sulindac metabolite levels in nipple aspirate fluid (NAF) after 6 weeks of treatment
Secondary Outcome Measure Information:
Title
Prostaglandin (PGE2) levels in NAF before and after 6 weeks of treatment
Title
NAG-1 induction and C-reactive protein (CRP) reduction before and after 6 weeks of treatment
Title
Magnitude of change and dose response of PGE2, NAG-1, and CRP in NAF before and after 6 weeks of treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia Thompson, PhD
Organizational Affiliation
University of Arizona
Official's Role
Study Chair
Facility Information:
Facility Name
Arizona Cancer Center at University of Arizona Health Sciences Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724-5024
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34112707
Citation
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.
Results Reference
derived

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

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