Clinical trial NCT00088972: S0300, Celecoxib in Preventing Breast Cancer in Premenopausal Women
Official title: Randomized Placebo-Controlled Biomarker Modulation Trial Using Celecoxib in Premenopausal Women at High Risk for Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: breast cancer
breast cancer in situ
lobular breast carcinoma in situ
ductal breast carcinoma
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-08-05
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Mammographic Density
timeFrame: 1 year
Secondary outcomes:
measure: Ki-67 Expression
timeFrame: 1 year
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Glendale Memorial Hospital Comprehensive Cancer Center
state: California
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Houston
country: United States
facility: St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: Veterans Affairs Medical Center - Houston
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
Study officials:
affiliation: Baylor College of Medicine
name: Powel H. Brown, MD, PhD
role: STUDY_CHAIR
References: