Exemestane With Celecoxib as Neoadjuvant Treatment in Postmenopausal Women With Stage II, III, and IV Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Stephen Povoski, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00201773
First received: September 12, 2005
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

To test whether the addition of the COX-2 inhibitor, celecoxib, will decrease the gene expression of CYP19 in breast cancers collected from postmenopausal women that receive neoadjuvant exemestane.


Condition Intervention Phase
Breast Cancer
Drug: Exemestane
Drug: Celecoxib
Other: Correlative studies
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Exemestane (Aromasin) in Combination With Celecoxib (Celebrex) as Neoadjuvant Treatment in Postmenopausal Women With Stage II, III, and IV Breast Cancer

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Determine if the addition of COX-2 inhibitor, celecoxib, will decrease the gene expression of CYP19 in breast cancer. [ Time Frame: up to 16 weeks ] [ Designated as safety issue: No ]
    Collected from postmenopausal women that receive neoadjuvant exemestane.


Secondary Outcome Measures:
  • Evaluate response rate and side effects of neoadjuvant exemestane and celecoxib in postmenopausal women. [ Time Frame: up to 16 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: July 2003
Study Completion Date: June 2011
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exemestane & Celecoxib
Patients will receive exemestane 25 mg orally per day for 8 weeks. Starting in the 9th week, patients will receive celecoxib 400 mg orally twice per day for 8 weeks in addition to exemestane.
Drug: Exemestane
25 mg orally once per day for 16 weeks.
Other Name: Aromasin
Drug: Celecoxib
given orally at two 200 mg capsules (400 mg) twice per day. Patients assigned to receive 400 mg twice per day should be instructed to take the drug with food.
Other Name: Celebrex
Other: Correlative studies
Other Names:
  • biopsy
  • tissue specimens
  • tissue samples

Detailed Description:

Rationale: In postmenopausal women, the main source of estrogen is through the conversion of androgens, or sex hormones produced by the adrenal glands. An enzyme called aromatase carries out this process. Exemestane, an aromatase inhibitor, blocks production of estrogens. Research indicates that the gene responsible for aromatase activity is CYPO19. Therefore, exemestane helps to inhibit aromatase activity through CYP019. Along with CYP019, another gene associated with breast cancer is an overexpression of COX-2 enzymes. Research suggests that COX-2 overexpression can cause cancer cell division, increased blood flow to tumors, and metastases. Celecoxib blocks COX-2 activity and produces fewer side effects compared with other non-steroidal inflammatory drugs (NSAIDs). This study builds on previous research to test the combination of exemestane and celecoxib for breast cancer.

Purpose: This study is evaluating the safety and efficacy of exemestane and celecoxib before surgery for stage II, III, and IV breast cancer in postmenopausal women. Tests will analyze the CYP019 gene after these treatments.

Treatment: Patients in this study will receive exemestane and celecoxib. Both drugs will be given to patients as oral pills. Exemestane will be taken daily for sixteen weeks. Starting in week 9, celecoxib will be taken twice daily for eight weeks. Therefore, during weeks 9-16, patients will be taking both exemestane and celecoxib. Several tests and exams will be given throughout the study to closely monitor patients, including a biopsy performed after the first 8 weeks on exemestane. After sixteen weeks on exemestane and celecoxib, patients will have breast surgery.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be female with histologically confirmed breast cancer
  • Stage II-IV disease
  • ER and/or PR positive
  • ECOG Performance Status 0-1
  • Tumor must be present following core needle biopsy as determined by physical exam or radiographic evaluation.
  • Postmenopausal
  • No prior treatment for current breast cancer. No other active malignancy is allowed.Adequately treated basal cell, squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for 5 years is permitted. Biphosphonates and palliative radiation for bone metastasis is permitted while on study.
  • Hormone replacement therapy must be discontinued. It is not permitted during the time on study.

Exclusion Criteria:

  • Known history of aspirin or NSAID induced asthma, urticaria or allergic reactions; or allergy to sulfonamides severe enough in nature to require emergency room treatment or hospitalization.
  • History of myocardial infarction or other thrombotic events.
  • Inflammatory breast cancer (edema or ulceration of the skin of the breast).
  • Significant renal dysfunction (serum creatinine > 1.5 x upper limit of normal).
  • Significant hepatic dysfunction (serum bilirubin > 1.5 x upper limit of normal or AST, ALT > 3 x upper limit of normal)
  • ANC <1.5, platelets <100,000 K/uL, and hemoglobin < 9 g/dL.
  • Use of other COX-2 inhibitors such as rofecoxib (Vioxx®, aspirin, trisalicylate (Trilisate®), is not permitted during the time on study. No washout period is required. Baby aspirin, 81 mg po daily, is permitted.
  • Use of NSAID's such as ibuprofen (Advil® or Motrin®), naproxyn (Aleve® Naprosyn®, or Anaprox®), etodolac (Lodine®), oxaprozin (Daypro®), difusanil (Dolobid®), nabumetone (Relafin®), or tolmetin (Tolectin®) is not permitted during the time on study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00201773

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Pfizer
Investigators
Principal Investigator: Stephen Povoski Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Stephen Povoski, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00201773     History of Changes
Other Study ID Numbers: OSU-0245
Study First Received: September 12, 2005
Last Updated: September 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
Post-Menopause
Neoadjuvant Therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Celecoxib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 16, 2014