<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02252978</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00028209</org_study_id>
    <secondary_id>NCI-2014-01594</secondary_id>
    <secondary_id>CCCWFU 99712</secondary_id>
    <secondary_id>P30CA012197</secondary_id>
    <nct_id>NCT02252978</nct_id>
  </id_info>
  <brief_title>Ciprofloxacin Compared to Placebo in Diagnosing Prostate Cancer in Patients Undergoing Prostate Biopsy</brief_title>
  <official_title>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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies ciprofloxacin compared to an inactive treatment (placebo) in&#xD;
      diagnosing prostate cancer in patients undergoing removal of prostate cells or tissues for&#xD;
      examination (biopsy). Ciprofloxacin is an antibiotic, a type of drug used to treat infections&#xD;
      caused by bacteria. Giving ciprofloxacin to patients undergoing a prostate biopsy may help to&#xD;
      lower abnormal prostate-specific antigen (PSA) levels caused by bacterial infection of the&#xD;
      prostate gland and may or may not affect the detection rate of prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the non-inferiority of the rate of detection of prostate cancer in men with&#xD;
      decreased serum PSA values treated with placebo compared to ciprofloxacin prior to prostate&#xD;
      biopsy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the change in PSA from randomization to biopsy in men treated with&#xD;
      ciprofloxacin versus those treated with placebo.&#xD;
&#xD;
      II. To compare the rates of post-biopsy complications (including duration of hematuria,&#xD;
      hematochezia, hematospermia, fever &gt; 101°F, and hospital admission rates related to biopsy,&#xD;
      sepsis, and pain) between men treated with ciprofloxacin versus those treated with placebo.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To determine if benign prostatic hyperplasia (BPH) or erectile dysfunction are associated&#xD;
      with abnormal PSA or prostatic inflammation reported in the biopsy specimen.&#xD;
&#xD;
      II. To determine the correlation between change in PSA from randomization to biopsy and&#xD;
      urinalysis pre- and post-ciprofloxacin versus placebo.&#xD;
&#xD;
      III. To determine the correlation between change in PSA and prostate massage pre- and&#xD;
      post-ciprofloxacin versus placebo.&#xD;
&#xD;
      IV. To determine the qualitative and quantitative difference in flora (ciprofloxacin&#xD;
      resistant organisms) obtained from rectal swab pre- and post- two week course of&#xD;
      ciprofloxacin vs. placebo.&#xD;
&#xD;
      V. To correlate prostate symptom severity (International Prostate Symptom Score [IPSS]) with&#xD;
      erectile function (International Index of Erectile Function [IIEF-5]) at baseline.&#xD;
&#xD;
      VI. To correlate urinary, prostate massage or rectal swab findings to pathology findings&#xD;
      including cancer, inflammation, prostatic intra-epithelial neoplasia (PIN), atypical acinar&#xD;
      proliferation (ASAP) or other findings at the end of the study.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive ciprofloxacin orally (PO) twice daily (BID) for 2 weeks.&#xD;
&#xD;
      ARM II: Patients receive ciprofloxacin PO BID for 2 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No funding support&#xD;
  </why_stopped>
  <start_date type="Actual">July 2016</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prostate cancer detection rates</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in PSA</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of post-biopsy complications (including duration of hematuria, hematochezia, hematospermia, fever &gt; 101°F, and hospital admission rates related to biopsy, sepsis, and pain)</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>Will be compared between groups using Chi-square tests (or Fisher's Exact tests if the expected cell counts are below 5).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>BPH or erectile dysfunction</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>In order to determine if BPH or erectile dysfunction are associated with abnormal PSA or prostatic inflammation reported in the biopsy specimen, 2x2 Chi Square tests will be used where each measure will be dichotomized. In addition, the consistency of these associations across the two treatment groups will be examined using a 3-way table and examining the Breslow Day test to see whether the odds ratios for each treatment are comparable.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in urinalysis pre- and post-treatment</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>In order to determine the correlation between change in PSA from randomization to biopsy and urinalysis pre- and post-ciprofloxacin, the Pearson correlations of the change in PSA with white blood cells pre- and post-ciprofloxacin vs. placebo will be estimated. If the data is found to be non-normal the Spearman rank correlations will be used for this analysis.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in prostate massage outcomes</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>The correlation between change in PSA and prostate massage pre- and post-ciprofloxacin vs placebo will be determined. Will examine whether there is a significant difference in PSA changes between the ciprofloxacin group and placebo group for different prostate massage outcomes using a 2-way analysis of variance (ANOVA) model. Will consider creating contrasts within the ANOVA model to test whether there is an ordered (possibly linear) relationship between levels of prostate massage and PSA change values (i.e., fitting a one-degree of freedom contrast within the ANOVA models).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in flora levels</measure>
    <time_frame>2 weeks</time_frame>
    <description>In order to determine the qualitative and quantitative difference in flora obtained from rectal swab pre- and post- two week course of ciprofloxacin vs. placebo 2-sample t-tests will be used to compare the change in these measures (for quantitative measures) and 2x2 Chi-Square tests to examine qualitative changes (Improve Yes/no by treatment group).</description>
  </other_outcome>
  <other_outcome>
    <measure>Prostate symptom severity (IPSS) and erectile function (IIEF-5)</measure>
    <time_frame>Day 1</time_frame>
    <description>To assess the correlation between prostate symptom severity (IPSS) and erectile function (IIEF-5) at baseline to ciprofloxacin or placebo treatment, an analysis of covariance model will be fit that examines the follow-up measure (IPSS) as the outcome, with the treatment indicator and IIEF-5 measure as predictors and their interaction included to see if the relationship depends on treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pathology findings</measure>
    <time_frame>Up to 1 month</time_frame>
    <description>In order to correlate urinary, prostate massage or rectal swab findings to pathology findings including cancer, inflammation, prostatic intra-epithelial neoplasia, atypical acinar proliferation or other findings will either estimate Pearson or Spearman correlations (depending on the distribution of the measures) or one measure is binary (i.e., cancer yes/no) then will examine 2-sample t-tests.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Arm I (ciprofloxacin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ciprofloxacin PO BID for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive placebo PO BID for 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ciprofloxacin</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (ciprofloxacin)</arm_group_label>
    <other_name>Cipro</other_name>
    <other_name>CPFX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <other_name>PLCB</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>quality-of-life assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (ciprofloxacin)</arm_group_label>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <other_name>quality of life assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (ciprofloxacin)</arm_group_label>
    <arm_group_label>Arm II (placebo)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Abnormal serum PSA (total &gt; 2.5 ng/ml or other clinically important biomarker&#xD;
             parameters, including PSA velocity and density) associated with or without normal&#xD;
             digital rectal examination&#xD;
&#xD;
          -  Men who have elected to proceed with a diagnostic prostate biopsy&#xD;
&#xD;
          -  Any prostate size&#xD;
&#xD;
          -  Willingness and ability to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of prostate cancer&#xD;
&#xD;
          -  Urine culture positive for significant urinary tract infection (UTI)&#xD;
&#xD;
          -  A history of antibiotic use within one month prior to initial PSA level measurement&#xD;
&#xD;
          -  Allergy to fluoroquinolones&#xD;
&#xD;
          -  Currently taking imperative medications with significant drug-drug interaction with&#xD;
             ciprofloxacin&#xD;
&#xD;
          -  Compromised renal function with estimated glomerular filtration rate (GFR) of &lt; 30&#xD;
             ml/min/1.73m^2&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>K. C. Balaji</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Veterans Administration Medical Center.</name>
      <address>
        <city>Salisbury</city>
        <state>North Carolina</state>
        <zip>28144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Center of Wake Forest University</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>July 3, 2018</last_update_submitted>
  <last_update_submitted_qc>July 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciprofloxacin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02252978
org study id: IRB00028209
secondary id: NCI-2014-01594
secondary id: CCCWFU 99712
secondary id: P30CA012197
nct id: NCT02252978
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Prostate cancer detection rates
time frame: Up to 8 weeks
description: 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.
measure: Change in PSA
time frame: Up to 8 weeks
description: 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.
measure: Rates of post-biopsy complications (including duration of hematuria, hematochezia, hematospermia, fever > 101°F, and hospital admission rates related to biopsy, sepsis, and pain)
time frame: Up to 8 weeks
description: Will be compared between groups using Chi-square tests (or Fisher's Exact tests if the expected cell counts are below 5).
measure: BPH or erectile dysfunction
time frame: Up to 8 weeks
description: In order to determine if BPH or erectile dysfunction are associated with abnormal PSA or prostatic inflammation reported in the biopsy specimen, 2x2 Chi Square tests will be used where each measure will be dichotomized. In addition, the consistency of these associations across the two treatment groups will be examined using a 3-way table and examining the Breslow Day test to see whether the odds ratios for each treatment are comparable.
measure: Change in urinalysis pre- and post-treatment
time frame: Up to 8 weeks
description: In order to determine the correlation between change in PSA from randomization to biopsy and urinalysis pre- and post-ciprofloxacin, the Pearson correlations of the change in PSA with white blood cells pre- and post-ciprofloxacin vs. placebo will be estimated. If the data is found to be non-normal the Spearman rank correlations will be used for this analysis.
measure: Change in prostate massage outcomes
time frame: Up to 8 weeks
description: The correlation between change in PSA and prostate massage pre- and post-ciprofloxacin vs placebo will be determined. Will examine whether there is a significant difference in PSA changes between the ciprofloxacin group and placebo group for different prostate massage outcomes using a 2-way analysis of variance (ANOVA) model. Will consider creating contrasts within the ANOVA model to test whether there is an ordered (possibly linear) relationship between levels of prostate massage and PSA change values (i.e., fitting a one-degree of freedom contrast within the ANOVA models).
measure: Change in flora levels
time frame: 2 weeks
description: In order to determine the qualitative and quantitative difference in flora obtained from rectal swab pre- and post- two week course of ciprofloxacin vs. placebo 2-sample t-tests will be used to compare the change in these measures (for quantitative measures) and 2x2 Chi-Square tests to examine qualitative changes (Improve Yes/no by treatment group).
measure: Prostate symptom severity (IPSS) and erectile function (IIEF-5)
time frame: Day 1
description: To assess the correlation between prostate symptom severity (IPSS) and erectile function (IIEF-5) at baseline to ciprofloxacin or placebo treatment, an analysis of covariance model will be fit that examines the follow-up measure (IPSS) as the outcome, with the treatment indicator and IIEF-5 measure as predictors and their interaction included to see if the relationship depends on treatment.
measure: Pathology findings
time frame: Up to 1 month
description: In order to correlate urinary, prostate massage or rectal swab findings to pathology findings including cancer, inflammation, prostatic intra-epithelial neoplasia, atypical acinar proliferation or other findings will either estimate Pearson or Spearman correlations (depending on the distribution of the measures) or one measure is binary (i.e., cancer yes/no) then will examine 2-sample t-tests.
arm group label: Arm I (ciprofloxacin)
arm group type: Experimental
description: Patients receive ciprofloxacin PO BID for 2 weeks.
arm group label: Arm II (placebo)
arm group type: Placebo Comparator
description: Patients receive placebo PO BID for 2 weeks.
intervention type: Drug
intervention name: ciprofloxacin
description: Given PO
arm group label: Arm I (ciprofloxacin)
other name: Cipro
other name: CPFX
intervention type: Other
intervention name: placebo
description: Given PO
arm group label: Arm II (placebo)
other name: PLCB
intervention type: Other
intervention name: quality-of-life assessment
description: Ancillary studies
arm group label: Arm I (ciprofloxacin)
arm group label: Arm II (placebo)
other name: quality of life assessment
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Arm I (ciprofloxacin)
arm group label: Arm II (placebo)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: K. C. Balaji
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Ciprofloxacin