Breast Cancer
Conditions
Keywords
breast cancer, breast cancer in situ, lobular breast carcinoma in situ, ductal breast carcinoma
Brief summary
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
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.
Interventions
DRUGcelecoxib
Given orally
OTHERplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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% 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mammographic Density | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ki-67 Expression | 1 year | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive oral celecoxib twice daily for 12 months in the absence of unacceptable toxicity or diagnosis of cancer. | 3 |
| Arm II Patients receive oral placebo twice daily for 12 months in the absence of unacceptable toxicity or diagnosis of cancer. | 5 |
| Total | 8 |
Baseline characteristics
| Characteristic | Arm I | Total | Arm II |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 8 Participants | 5 Participants |
| Age, Continuous | 43.8 years STANDARD_DEVIATION 3.9 | 43.5 years STANDARD_DEVIATION 4.9 | 43.3 years STANDARD_DEVIATION 5.9 |
| Region of Enrollment United States | 3 participants | 8 participants | 5 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 0 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 5 |
Outcome results
Primary
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.
Time frame: 1 year
Population: Counts represent number of patients for by arm for whom a 1 year mammographic density image was submitted. However, since the study was closed early due to poor accrual, there was insufficient accrual to evaluate study endpoints, and these images were never analyzed.
Secondary
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).
Time frame: 1 year
Population: Since the study was closed early due to insufficient accrual, the ki-67 data were never collected.