S0300, Celecoxib in Preventing Breast Cancer in Premenopausal Women

• ClinicalTrials.gov Identifier: NCT00088972
• Recruitment Status: Terminated
• First Posted: August 5, 2004
• Results First Posted: April 9, 2013
• Last Update Posted: August 10, 2018
• Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Southwest Oncology Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: celecoxib; Other: placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Randomized Placebo-Controlled Biomarker Modulation Trial Using Celecoxib in Premenopausal Women at High Risk for Breast Cancer
• Study Start Date: November 2004
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I - Celecoxib; Patients receive oral celecoxib twice daily for 12 months in the absence of unacceptable toxicity or diagnosis of cancer.	Drug: celecoxib; Given orally
Placebo Comparator: Arm II - Placebo; Patients receive oral placebo twice daily for 12 months in the absence of unacceptable toxicity or diagnosis of cancer.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures :

1. Mammographic Density [ Time Frame: 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 Outcome Measures :

1. Ki-67 Expression [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Glendale Memorial Hospital Comprehensive Cancer Center

Glendale, California, United States, 91204

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131-5636

United States, Texas

Baylor University Medical Center - Houston

Houston, Texas, United States, 77030

Ben Taub General Hospital

Houston, Texas, United States, 77030

Methodist Hospital

Houston, Texas, United States, 77030

St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital

Houston, Texas, United States, 77030

Veterans Affairs Medical Center - Houston

Houston, Texas, United States, 77030

United States, Washington

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States, 98122-4307

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States, 98195-6043

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

• Study Chair: Powel H. Brown, MD, PhD; Baylor College of Medicine

More Information

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00088972
• Other Study ID Numbers: CDR0000377698; U10CA012027 ( U.S. NIH Grant/Contract ); S0300 ( Other Identifier: SWOG ); U10CA037429 ( U.S. NIH Grant/Contract )
• First Posted: August 5, 2004
• Results First Posted: April 9, 2013
• Last Update Posted: August 10, 2018
• Last Verified: July 2018

Keywords provided by Southwest Oncology Group:

breast cancer; breast cancer in situ; lobular breast carcinoma in situ; ductal breast carcinoma

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Celecoxib; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action