Clinical trial NCT00201773: Exemestane With Celecoxib as Neoadjuvant Treatment in Postmenopausal Women With Stage II, III, and IV Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Post-Menopause
Neoadjuvant Therapy
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2005-09-20
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Number of Patients With Decreased Gene Expression of CYP19 in Breast Cancer by Adding COX-2 Inhibitor to Exemestane
timeFrame: up to 16 weeks
Secondary outcomes:
measure: Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women.
timeFrame: up to 16 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Stephen Povoski
role: PRINCIPAL_INVESTIGATOR
References: