S0300, Celecoxib in Preventing Breast Cancer in Premenopausal Women

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of celecoxib may be effective in preventing breast cancer. PURPOSE: This randomized phase II trial is studying how well celecoxib works in preventing breast cancer in premenopausal women who are at risk for developing the disease.

Detailed Description
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OBJECTIVES: Compare 1-year mammographic density in premenopausal women at high risk for developing breast cancer treated with celecoxib vs placebo. Compare 1-year proliferation of breast epithelial cells, as measured by Ki67 staining, in patients treated with these drugs. Compare the expression of other biomarkers, including cyclo-oxygenase-2 (COX-2) enzyme and a marker of apoptosis, in breast tissue of patients treated with these drugs. Compare 1-year plasma levels of insulin-like growth factor (IGF)-1, IGF binding protein-3, and prostaglandin E_2 in patients treated with these drugs. Compare the toxicity of these drugs in these patients. OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to risk category (lobular carcinoma in situ or ductal carcinoma in situ vs BRCA1/2 mutation AND any Gail risk vs Gail risk ≥1.7% but < 5% vs Gail risk ≥ 5%) and prior tamoxifen use (yes vs no). Patients are randomized to 1 of 2 treatment arms. Celocoxib: Patients receive oral celecoxib twice daily. Placebo: Patients receive oral placebo twice daily. In both arms, treatment continues for 12 months in the absence of unacceptable toxicity or diagnosis of cancer. Patients are followed at 1 month. PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Official Title
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Randomized Placebo-Controlled Biomarker Modulation Trial Using Celecoxib in Premenopausal Women at High Risk for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: celecoxib
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: At elevated risk of developing breast cancer, as defined by 1 of the following: Modified Gail risk at 5 years ≥ 1.7% or lifetime risk ≥ 20% AND Claus Model, BRCAPro Model, or Tyrer-Cuzick Model lifetime risk ≥ 20% Diagnosis of lobular carcinoma in situ or ductal carcinoma in situ Known deleterious mutation of BRCA1 or BRCA2 At least 1 breast available for imagery and biopsy Has undergone a baseline mammogram with a standard density wedge within 7-14 days after completion of the last menstrual period AND within 7 days before study entry Mammogram normal or benign (BIRADS score 0 or 1) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Premenopausal, defined by 1 of the following criteria: Last menstrual period < 6 months ago AND no prior bilateral ovariectomy AND not on estrogen replacement therapy Prior hysterectomy (with ovaries still in place) AND normal follicle-stimulating hormone levels within 28 days of study entry Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin < 2.0 times institutional upper limit of normal (IULN) SGOT or SGPT < 2 times IULN Alkaline phosphatase < 2 times IULN INR ≤ 1.5 PT and PTT ≤ IULN Renal Serum creatinine < 2.0 times IULN Cardiovascular No history of myocardial infarction No angina pectoris No known coronary artery disease No history of stroke or mini-stroke (e.g., transient ischemic attack) No history of thromboembolic disease (e.g., deep vein thrombosis or pulmonary embolism) No uncontrolled hypertension (i.e., blood pressure > 140/90 mmHg) Pulmonary No asthma after taking aspirin or other NSAIDs Other No known sensitivity to celecoxib No allergy to sulfonamides No urticaria or allergic-type reactions after taking aspirin or other NSAIDs No extreme lactose intolerance No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or early bladder cancer (preinvasive transitional cell carcinoma of the bladder) Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy More than 5 years since prior biologic therapy for cancer Chemotherapy More than 5 years since prior chemotherapy for cancer Endocrine therapy At least 28 days since prior tamoxifen No prior systemic estrogen modifiers (SERMs) or aromatase inhibitors Concurrent hormonal contraception (i.e., pills, patches, or shots) allowed provided contraception was initiated prior to study entry Radiotherapy No prior radiotherapy to the breast to be studied Surgery Not specified Other At least 7 days since prior anticoagulant therapy More than 1 month since prior chronic daily aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) of more than 7 days duration Concurrent intermittent aspirin or NSAIDs allowed (no more than 10 days per month) No concurrent participation in another clinical trial for treatment or prevention of cancer unless no longer receiving treatment and is in the follow-up phase

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I - Celecoxib<br>Patients receive oral celecoxib twice daily for 12 months in the absence of unacceptable toxicity or diagnosis of cancer. | Drug: celecoxib<br>* Given orally<br>|
| Placebo Comparator: Arm II - Placebo<br>Patients receive oral placebo twice daily for 12 months in the absence of unacceptable toxicity or diagnosis of cancer. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mammographic Density | The primary outcome measure is change in mammographic density. The null hypothesis is that there is no difference between the arms in change in mammographic density over one year versus the alternative that the treatment arm reduces mammographic density by 10 points (percent of pixels highlighted) or more over one year compared to the change in the placebo arm. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ki-67 Expression | The difference between the two arms in the percent of patients with non-zero ki-67 expression over the two time periods (baseline and 1-year). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, breast cancer in situ, lobular breast carcinoma in situ, ductal breast carcinoma