Pre-Prostatectomy Celecoxib or Placebo

Randomized Study of Pre-Prostatectomy Celecoxib or Placebo

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer; Adenocarcinoma of the Prostate
• Intervention / Treatment: Drug: Placebo; Drug: Celecoxib

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

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute
    • Portland, Oregon, United States, 97207
      • Portland VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Celecoxib; Treated patients will receive 4 weeks of celecoxib at 400 mg twice daily by mouth	Drug: Celecoxib; Selective inhibition of COX-2 without significant cyclooxygenase-1 (COX-1) inhibition; Other Names: Celebrex; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]; Benzenesulfonamide
Placebo Comparator: Placebo; Control patients will receive a suitable placebo for 4 weeks, twice daily by mouth	Drug: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: Pfizer
• Investigators: Principal Investigator: Tomasz M Beer, MD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 18, 2016
• First Posted (Estimate): July 21, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: prostate cancer; chemoprevention; celecoxib; NSAIDs; COX-2 inhibitors
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic 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; Carbonic Anhydrase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib; Benzenesulfonamide
• Other Study ID Numbers: IRB00001004; HOR-01019-L (Other Identifier: OHSU Knight Cancer Institute)