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Study Summary
No. ID02-458:.......Breast......Banu Arun......Breast Medical Oncology
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Study Summary Title
Study Summary
Number:
ID02-458
Study Title:Pilot Study of Biomarker Modulation with a COX-2 Inhibitor using Ductal Lavage in Women at Increased Risk for Breast Cancer
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Physician New Patient Referral
Name:Banu ArunPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Breast Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2817
Contact us about clinical trials
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General Information
Disease Group:BreastSupported By:N/A
Phase of Study:Phase IIReturn
Visit:
2 Return visits. Months 3 and 6.
Treatment
Agents:
CelecoxibHome Care:Subjects will self administer Celecoxib, 400 mg BID
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if Celebrex (celecoxib)
can cause changes in the breast tissue of women who are at increased risk to
develop breast cancer. Our goal is also to develop an easy method to obtain
breast cells from the breast of women who are at increased risk to develop
breast cancer.
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Study Objectives / Outcomes
    Our goal is to test, in a pilot fashion, the modulation of biomarkers in response to celecoxib in breast tissue of women who are at high risk for breast cancer and to develop a non invasive tissue acquisition method for our subsequently planned phase II placebo controlled chemoprevention study. Our hypothesis is that treatment with a COX-2 inhibitor will modulate proliferation and apoptotic markers in breast tissue of women who are at high risk for breast cancer. Furthermore, we hypothesize that ductal lavage is a feasible method to collect breast epithelial cells for biomarker analyses.

    Demonstration of a decrease in Ki-67 and other proliferation markers, increase in apoptotic markers and reversal of atypia will provide us with preliminary data to proceed with our planned phase II, placebo controlled chemoprevention study with celecoxib. Ultimately, the development of non-hormonal chemopreventive agents, and identification of surrogate markers will allow us to plan large-scale, phase III chemoprevention studies with the endpoint of cancer incidence.
SPECIFIC AIMS
    Aim 1: To evaluate cyclooxygenase-2 inhibitor (celecoxib) induced modulation of cytologic atypia, proliferation (Ki-67, ER, COX-2, Her-2/neu, EGFR, p53) and apoptosis markers (bcl-2, 15-LOX) in breast tissue of women who are high risk to develop breast cancer.

    Aim 2a: To compare breast epithelial cell yield and cytologic morphology in specimens obtained via FNA versus ductal lavage.
    Aim 2b: To evaluate the feasibility of evaluating biomarkers in ductal lavage fluid obtained from breast tissue of women at high risk for breast cancer for the use of future chemopreventive interventions.

    Aim 3: To evaluate, as an exploratory endpoint, changes in proteomic pattern in serum and in specimens obtained via FNA /ductal lavage. Pre and post celecoxib treatment proteomics spectra in serum, FNA and ductal lavage will be compared.
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Study Status Information
Study Activation / Registration Date:03/05/2003
IRB Review and Approval Date:09/04/2002
Study Type:Cancer Control
Recruitment Status:Closed
Projected Accrual:56
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) The subject must be 21 years of age or older at the time of study entry

2) Subjects have a 5 year projected risk of breast cancer 1.67 (Gail model), or a history LCIS or a previous history of ER negative invasive breast cancer and have no evidence of disease after 2 years.

3) The subject must have been properly informed of the study and must sign an informed consent to be able to be enrolled in the study. The informed consent document must be signed, witnessed, and dated prior to start of the study.

4) Normal physical exam within last 6 months and no evidence of invasive breast cancer or any other active cancers

5) Within 6 months prior study, the subject must have a bilateral mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions.

6) Within 12 months prior to randomization a normal gynecologic exam, including a bimanual pelvic exam and, if indicated, a pap smear.

7) Subjects may be receiving non-hormonal medications.

8) Subjects at childbearing age must have a negative urine pregnancy test within 2 weeks prior to drug initiation.

9) Subjects of childbearing age must use non-hormonal methods of contraception (barrier methods, spermicides, surgical methods) for the duration of the study.

10) ECOG status of 0 – 2.

11) Subjects must have normal bone marrow, liver, and renal functions.

12) No ischemic heart disease and normal sinus rhythm on EKG.

Exclusion Criteria:1) Less than 21 years of age

2) Any type of active invasive cancer

3) Bilateral mastectomy

4) Known allergy to celebrex, aspirin, other NSAIDs or other COX-2 inhibitors, sulfa containing drugs

5) Past or current history of gastrointestinal bleeding, ulcer disease or perforation

6) Past or current history of liver or renal disease

7) Performance status that restricts normal activity for a significant portion of each day

8) Use of oral contraceptives; androgens; luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, or steroids. Women who discontinue these drugs at least 3 months prior to study enrollment will be eligible.

9) Psychiatric condition, including history of clinical depression, or addictive disorder that would preclude obtaining informed consent or would interfere with compliance.

10) Use of Celecoxib, tamoxifen, raloxifene, or other SERM therapy (women who discontinue the drugs at least 3 months prior to study enrollment are eligible).

11) Pregnant women or lactating women

12) Presence of saline or silicone breast implants

13) Active bleeding disorder such as qualitative or quantitative platelet abnormalities, hemophilia or von Willebrand syndrome.

14) Presence of ischemic heart disease or abnormal EKG

15) Concomitant Warfarin use

16) Concomitant administration of flucanazole and/or lithium

17) Known genetic predisposition (presence of BRCA1 or BRCA2 mutation)

18) History of cardiovascular diseases that might include one of the following: myocardial infraction, angina, coronary angioplasty, congestive heart failure, stroke, or coronary bypass surgery

19) Uncontrolled hypertension (i.e. - > 135/>85 mm Hg on three repeated measurements during the 6 weeks prior to enrollment on the study

20) Family history of premature coronary disease (i.e. - onset < 55 years of age)

21) Diagnosis of Diabetes

22) Uncontrolled hypercholesteremia [low-density lipoprotein cholesterol (LDL-C) > 130]. Hypercholesteremia needs to be controlled following the updated National Cholesterol Education Program Adult Treatment Panel III Guidelines for at least 3 months prior to enrollment on the study. Hypercholesteremia treatment should continue during the entire period of Celecoxib treatment on the protocol.

23) Smoking history during the 3-years prior to enrollment on the study

24) Metabolic syndrome diagnosis: The diagnosis of metabolic syndrome is made when three or more of these risk factors are present: a. Waist circumference: Men > 102 cm (>40 in.); Women > 88 cm (> 35 in.); b. Triglycerides = 150 mg/dl (=1.69 mmol/L); c. High-density lipoprotein cholesterol (HDL-C): [Men < 40 mg/dl (< 1.03 mmol/L), Women < 50 mg/dl (< 1.29 mmol/L)]; d. Blood pressure = 130/85 mm Hg; e. Fasting glucose = 110 mg/dl (= 6.1 mmol/L)

25) History of deep venous thrombosis, pulmonary embolism, systemic lupus erythematous, family history of protein S or C deficiencies, prior heparin-induced thrombocytopenia, Factor V Leiden deficiencies or high homocysteine levels

26) Any indications for ASA Deficiency

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Links
Registration Number: Not Registered

Other Links:
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Results


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