Adenocarcinoma of the Prostate, Prostate Cancer
Conditions
Keywords
prostate cancer, NSAIDs, chemoprevention, celecoxib, COX-2 inhibitors
Brief summary
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
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
Interventions
DRUGCelecoxib
Selective inhibition of COX-2 without significant cyclooxygenase-1 (COX-1) inhibition
DRUGPlacebo
Sponsors
Pfizer
OHSU Knight Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apoptosis Index, defined as the percent positive staining cells | approximately 4 weeks of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostaglandin and Androgen Receptor Levels | approximately 4 weeks of treatment | Descriptive statistical analysis will be conducted. The estimates will be reported with 95% confidence intervals. |
| Percent Change in Median PSA Values, pre- and postoperatively | approximately 4 weeks of treatment | Pre- and postoperative PSA will be collected. Descriptive statistics will be conducted, comparing preoperative PSA level to postoperative level. |
| Perioperative Analgesic Use, using morphine equivalents | Prostatectomy to discharge from hospital, no more than 30 days post prostatectomy | 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. |
| Surgical Complications, defined as incidence of adverse events determined to be related to surgery graded by NCI CTCAE version 2.0 | Intraoperatively to 30 days postoperatively | Intraoperative and post surgical complications will be collected and reported. |
| Incidence of Adverse Events, graded by NCI CTCAE version 2.0 | From start of treatment to 30 days post prostatectomy | Descriptive statistical analysis will be conducted |
Countries
United States
Outcome results
None listed