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: Phase II trial to study the effectiveness of celecoxib in preventing breast cancer in premenopausal women who are at risk for developing the disease.

Condition	Treatment or Intervention	Phase
Breast Cancer breast cancer in situ lobular breast carcinoma in situ	Drug: celecoxib  Procedure: biological response modifier therapy  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: enzyme inhibitor therapy  Procedure: prostaglandin inhibition	Phase II

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 vs 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.

• Arm I: Patients receive oral celecoxib twice daily.
• Arm II: 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• At elevated risk of developing breast cancer, as defined by 1 of the following:
• Modified Gail risk at 5 years ≥ 1.7%
• Diagnosis of lobular carcinoma
• Known deleterious mutation of or
• 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)
• No ductal carcinoma
• 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 upper limit of normal (ULN)
• SGOT or SGPT < 2 times ULN
• Alkaline phosphatase < 2 times ULN
• INR ≤ 1.5
• PT and PTT normal

Renal

• Creatinine < 2.0 times ULN

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 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
• 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 (more than 7 days duration) daily aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
• 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

Study chairs or principal investigators

Charles A. Coltman, MD,  Study Chair,  San Antonio Cancer Institute   

Study ID Numbers:  CDR0000377698; SWOG-S0300
Record last reviewed:  September 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088972
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-20