Ciprofloxacin Compared to Placebo in Diagnosing Prostate Cancer in Patients Undergoing Prostate Biopsy

Study Overview
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Brief Summary
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This phase II trial studies ciprofloxacin compared to an inactive treatment (placebo) in diagnosing prostate cancer in patients undergoing removal of prostate cells or tissues for examination (biopsy). Ciprofloxacin is an antibiotic, a type of drug used to treat infections caused by bacteria. Giving ciprofloxacin to patients undergoing a prostate biopsy may help to lower abnormal prostate-specific antigen (PSA) levels caused by bacterial infection of the prostate gland and may or may not affect the detection rate of prostate cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the non-inferiority of the rate of detection of prostate cancer in men with decreased serum PSA values treated with placebo compared to ciprofloxacin prior to prostate biopsy. SECONDARY OBJECTIVES: I. To compare the change in PSA from randomization to biopsy in men treated with ciprofloxacin versus those treated with placebo. II. To compare the rates of post-biopsy complications (including duration of hematuria, hematochezia, hematospermia, fever > 101°F, and hospital admission rates related to biopsy, sepsis, and pain) between men treated with ciprofloxacin versus those treated with placebo. TERTIARY OBJECTIVES: I. To determine if benign prostatic hyperplasia (BPH) or erectile dysfunction are associated with abnormal PSA or prostatic inflammation reported in the biopsy specimen. II. To determine the correlation between change in PSA from randomization to biopsy and urinalysis pre- and post-ciprofloxacin versus placebo. III. To determine the correlation between change in PSA and prostate massage pre- and post-ciprofloxacin versus placebo. IV. To determine the qualitative and quantitative difference in flora (ciprofloxacin resistant organisms) obtained from rectal swab pre- and post- two week course of ciprofloxacin vs. placebo. V. To correlate prostate symptom severity (International Prostate Symptom Score [IPSS]) with erectile function (International Index of Erectile Function [IIEF-5]) at baseline. VI. To correlate urinary, prostate massage or rectal swab findings to pathology findings including cancer, inflammation, prostatic intra-epithelial neoplasia (PIN), atypical acinar proliferation (ASAP) or other findings at the end of the study. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive ciprofloxacin orally (PO) twice daily (BID) for 2 weeks. ARM II: Patients receive ciprofloxacin PO BID for 2 weeks.

Official Title
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A Phase II, Double-Blind, Placebo-Controlled Prospective Randomized Clinical Trial Evaluating the Role of an Empiric 2-Week Course of Ciprofloxacin on Rates of Detection of Cancer by Prostate Biopsy in Men With Abnormal Serum Prostate Specific Antigen Found at Screening (PREP Trial)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: ciprofloxacin
* Other: placebo
* Other: quality-of-life assessment
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Abnormal serum PSA (total > 2.5 ng/ml or other clinically important biomarker parameters, including PSA velocity and density) associated with or without normal digital rectal examination Men who have elected to proceed with a diagnostic prostate biopsy Any prostate size Willingness and ability to give informed consent Exclusion Criteria: History of prostate cancer Urine culture positive for significant urinary tract infection (UTI) A history of antibiotic use within one month prior to initial PSA level measurement Allergy to fluoroquinolones Currently taking imperative medications with significant drug-drug interaction with ciprofloxacin Compromised renal function with estimated glomerular filtration rate (GFR) of < 30 ml/min/1.73m^2

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (ciprofloxacin)<br>Patients receive ciprofloxacin PO BID for 2 weeks. | Drug: ciprofloxacin<br>* Given PO<br>* Other names: CPFX;Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO BID for 2 weeks. | Other: placebo<br>* Given PO<br>* Other names: PLCB;Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate cancer detection rates | Will be compared between groups using a binomial test to compare rates in the two groups. Groups will also be compared using logistic regression models to adjust for any pre-treatment patient level characteristics. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PSA | The data will be analyzed on a logarithmic scale to stabilize the variance. The change in log PSA from randomization to biopsy will be compared between the two groups using a two-sample t-test. In addition, the baseline log PSA levels will be compared between the two groups and if they are found to be imbalanced a 1-way analysis of covariance will be used to compare groups by including the baseline pre-randomization log-PSA value as the covariate in the model. | Up to 8 weeks | 
| Rates of post-biopsy complications (including duration of hematuria, hematochezia, hematospermia, fever > 101°F, and hospital admission rates related to biopsy, sepsis, and pain) | Will be compared between groups using Chi-square tests (or Fisher's Exact tests if the expected cell counts are below 5). | Up to 8 weeks |