S0300, Celecoxib in Preventing Breast Cancer in Premenopausal Women

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Other: placebo; Drug: celecoxib

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91204
      • Glendale Memorial Hospital Comprehensive Cancer Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Methodist Hospital
    • Houston, Texas, United States, 77030
      • Veterans Affairs Medical Center - Houston
    • Houston, Texas, United States, 77030
      • Baylor University Medical Center - Houston
    • Houston, Texas, United States, 77030
      • St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
  • Washington
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Powel H. Brown, MD, PhD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: August 4, 2004
• First Submitted That Met QC Criteria: August 4, 2004
• First Posted (Estimate): August 5, 2004

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: July 13, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: breast cancer; breast cancer in situ; ductal breast carcinoma; lobular breast carcinoma in situ
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: CDR0000377698; U10CA012027 (U.S. NIH Grant/Contract); U10CA037429 (U.S. NIH Grant/Contract); S0300 (Other Identifier: SWOG)