Pre-Prostatectomy Celecoxib or Placebo

Study Overview
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Brief Summary
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This study will seek to determine if the downstream effects of cyclooxygenase-2 (COX-2) inhibition suggested by preclinical systems occur in human prostate cancer. To answer this question, men who have chosen prostatectomy will be randomly assigned to preoperative treatment with celecoxib or placebo for four weeks. Carefully collected tumor, premalignant, and benign prostate tissue will then be examined for apoptosis, androgen receptor and prostaglandin E2 levels. Tumor COX-2 expression will be correlated with observed treatment effects. The data generated by this study will serve as a foundation for the development of COX-2 targeted therapies for prostate cancer, will provide preliminary evidence for larger scale clinical trials aimed at treatment and prevention of prostate cancer, and will validate current preclinical models used to study COX-2 in prostate cancer.

Detailed Description
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PRIMARY OBJECTIVE I. To determine if COX-2 inhibition with celecoxib significantly increases apoptosis in human adenocarcinoma of the prostate. SECONDARY OBJECTIVES I. To determine if COX-2 inhibition with celecoxib reduces levels of Prostaglandin E2 and androgen receptor in fresh tumor tissue collected at prostatectomy II. To collect pre- and postoperative serum Prostate Specific Antigen (PSA) for exploratory analyses III. To determine the effect of celecoxib on adverse effects, perioperative surgical complications and post surgery analgesic use

Official Title
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Randomized Study of Pre-Prostatectomy Celecoxib or Placebo

Conditions
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Adenocarcinoma of the Prostate, Prostate Cancer

Intervention / Treatment
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* Drug: Celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically or cytologically proven adenocarcinoma of the prostate and planned prostatectomy Age >= 18 Performance status (ECOG <= 2) Hemoglobin > 10 g/dL (within 4 weeks) Creatinine <= 1.5 mg/dL Signed informed patient consent Exclusion Criteria: Other preoperative or prior treatment directed at prostate cancer Significant active medical illness which in the opinion of the investigator would preclude protocol treatment Use of non-steroidal anti-inflammatory agents within seven days of celecoxib treatment Hypersensitivity to celecoxib A history of asthma, urticaria, or anaphylaxis precipitated by an NSAID History of significant upper gastrointestinal bleeding or active peptic ulcer disease Current treatment with anticoagulants Allergy to sulfonamide

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Celecoxib<br>Treated patients will receive 4 weeks of celecoxib at 400 mg twice daily by mouth | Drug: Celecoxib<br>* Selective inhibition of COX-2 without significant cyclooxygenase-1 (COX-1) inhibition<br>* Other names: Benzenesulfonamide;|
| Placebo Comparator: Placebo<br>Control patients will receive a suitable placebo for 4 weeks, twice daily by mouth | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apoptosis Index, defined as the percent positive staining cells | Percent positively staining cells with a minimum of 1000 total cells counted. Descriptive statistics will be conducted. The apoptotic index will be reported with 95% confidence intervals. | approximately 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostaglandin and Androgen Receptor Levels | Descriptive statistical analysis will be conducted. The estimates will be reported with 95% confidence intervals. | approximately 4 weeks of treatment | 
| Percent Change in Median PSA Values, pre- and postoperatively | Pre- and postoperative PSA will be collected. Descriptive statistics will be conducted, comparing preoperative PSA level to postoperative level. | approximately 4 weeks of treatment | 
| Perioperative Analgesic Use, using morphine equivalents | Descriptive statistical analysis will be conducted. The estimate will be calculated using morphine equivalents dividend by length of hospital stay and reported with 95% confidence intervals. | Prostatectomy to discharge from hospital, no more than 30 days post prostatectomy | 
| Surgical Complications, defined as incidence of adverse events determined to be related to surgery graded by NCI CTCAE version 2.0 | Intraoperative and post surgical complications will be collected and reported. | Intraoperatively to 30 days postoperatively | 
| Incidence of Adverse Events, graded by NCI CTCAE version 2.0 | Descriptive statistical analysis will be conducted | From start of treatment to 30 days post prostatectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, NSAIDs, chemoprevention, celecoxib, COX-2 inhibitors