For Cause Prostate Biopsy in REDUCE Population Trial

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Stephen Jones, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01529086
First received: January 31, 2012
Last updated: February 7, 2012
Last verified: January 2012
  Purpose

The REDUCE trial was conducted to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease. Dutasteride was compared with placebo for 4 years period. Results showed a relative risk reduction of 22.8 % (95% CI: 15.2 to 29.8)in prostate cancer.

For REDUCE, biopsies were defined as "protocol biopsy" if performed at certain timeframes, and "for cause" if outside these predetermined timeframes.

The investigators propose a post hoc analysis that would allow them to include biopsies that really justified a clinical indication, but were excluded from "for cause" analysis based on occurring at either the 2 or 4 year timeframes.

Thus the investigators propose analysis of both REDUCE groups by every yearly timeframe as:

Group 1--dutasteride group biopsied "for cause" using several definitions: biopsy of patients who received dutasteride whose PSA rose from nadir as defined in your own protocol,who had a PSA rise>0.2 ng/ml or who had a new abnormal DRE or had a free PSA<12% . The investigators define these as such because this would reasonably instigate biopsy if the clinician had a patient with this scenario in the non-study setting.

Group 2--placebo group biopsied "for cause" using several definitions, regardless of timeframe but reported at each year of the study and aggregate, with the aggregate number being the primary outcome. Thus the investigators would request results of biopsy of patients who received placebo To establish differences in biopsy positive rates the groups as per each definition listed, to determine if dutasteride decreased the likelihood of "for cause" biopsy compared to "not for cause" biopsy, and if there is a difference in cancer detection risk rate depending on cause vs. no cause in that group compared to placebo.


Condition
Early Detection of Cancer

Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Determining the Likelihood of Prostate Cancer Detection in Men Taking Dutasteride When Biopsy is Performed 'for Cause'.

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Cancer detection risk among the groups in the "for cause" context [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Determination of differences in cancer detection risk rate depending on cause vs no cause in that group compared to placebo


Secondary Outcome Measures:
  • Dutasteride as a key factor in the likelihood of "for cause" biopsy [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Determination of dutasteride as an item in decreasing the likelihood of "for cause" biopsy compared to "not for cause" biopsy


Enrollment: 6729
Study Start Date: February 2012
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Group 1

Subjects have to meet the following criteria:

  1. A rise in PSA from nadir at any time post-nadir
  2. PSA change from baselin >0.2 mg/ml at any time post-baseline
  3. Abnormal DRE at any time post-baseline
  4. Free-PSA <12% at any time post-baseline
  5. At least one of the above 4 criteria
Group 2

Patients on placebo treatment that meet the following criteria:

  1. Change from baseline PSA between 0.0 and 0.35 (ie, 0.0 ≤ change from baseline PSA < 0.35) at any time post-baseline. Note that in REDUCE PSA was recorded to the nearest 0.1.
  2. Abnormal DRE at any time post-baseline
  3. Change from baseline PSA ≥ 0.35 at any time post-baseline
  4. Change from baseline PSA ≥ 0.75 at any time post-baseline
  5. PSA ≥ 2.5 at any time post-baseline
  6. PSA ≥ 4.0 at any time post-baseline
  7. Percent Free PSA < 12% at any time post-baseline
  8. At least one of the above 7 criteria.
Group 3
Subjects in the dutasteride treatment group who did not meet any of the 4 dutasteride criteria (ie, dutasteride subjects not in Group 1e).
Group 4
Subjects in the placebo treatment group who did not meet any of the 7 placebo criteria (ie, placebo subjects not in Group 2h).

Detailed Description:

Purpose: Determining the likelihood of prostate cancer detection in men taking dutasteride when biopsy is performed 'for cause'.

Population: The population of interest is the REDUCE Biopsied population, that is, all subjects in the Efficacy population who have at least one post-baseline biopsy reviewed by the Central Pathology Laboratory.

Analyses: Initial interest will be focused on data from the Year 1-2 time period, to avoid the potential effect of the cancer diagnoses from the Year 2 scheduled biopsies on the assessments utilized in the "for cause" definitions. Only PSA data from Years 1-2 and baseline will be utilized in the computation of the various PSA metrics, and only Central Pathology results from Years 1-2 will be utilized to establish post-baseline diagnoses. PSA values on or within 42 days after date of biopsy will be excluded from the analyses, to avoid potential effects of biopsy on the PSA value.

For each of the 4 groups of subjects, the following will be summarized: number of subjects meeting the corresponding criteria, number and % of subjects diagnosed with prostate cancer, number and % of such subjects diagnosed with Gleason 7-10, and number and % of subjects diagnosed with either prostate cancer, HGPIN or ASAP. Summaries of the numbers of subjects meeting each of the specific criteria for group 1 (a through e) and Group 2 (a through h) will be provided.

In addition, summaries investigating the effect of baseline variables (such as age, family history of prostate cancer, prostate volume, percent free PSA, number of cores at the entry biopsy) on the occurrence of prostate cancer diagnoses and Gleason 7-10 diagnoses may be developed.

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

REDUCE trial participants

Criteria

Inclusion Criteria:

Group 1—subjects in the dutasteride treatment group who meet the following sets of criteria:

  • A rise in PSA from nadir at any time post-nadir
  • PSA change from baseline >0.2 ng/ml at any time post-baseline
  • Abnormal DRE at any time post-baseline
  • Free PSA<12% at any time post-baseline
  • At least one of the above 4 criteria.

Group 2—subjects in the placebo treatment group who meet the following sets of criteria:

  • Change from baseline PSA between 0.0 and 0.35 (ie, 0.0 ≤ change from baseline PSA < 0.35) at any time post-baseline. Note that in REDUCE PSA was recorded to the nearest 0.1.
  • Abnormal DRE at any time post-baseline
  • Change from baseline PSA ≥ 0.35 at any time post-baseline
  • Change from baseline PSA ≥ 0.75 at any time post-baseline
  • PSA ≥ 2.5 at any time post-baseline
  • PSA ≥ 4.0 at any time post-baseline
  • Percent Free PSA < 12% at any time post-baseline
  • At least one of the above 7 criteria.

Group 3--subjects in the dutasteride treatment group who did not meet any of the 4 dutasteride criteria (ie, dutasteride subjects not in Group 1e).

Group 4--subjects in the placebo treatment group who did not meet any of the 7 placebo criteria (ie, placebo subjects not in Group 2h).

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01529086

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
GlaxoSmithKline
Investigators
Principal Investigator: Stephen Jones, MD The Cleveland Clinic
  More Information

Publications:
Responsible Party: Stephen Jones, Chairman of Department of Regional Urology, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01529086     History of Changes
Other Study ID Numbers: REDUCE-FOR CAUSE, 115686
Study First Received: January 31, 2012
Last Updated: February 7, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by The Cleveland Clinic:
prostate cancer
dutasteride
for cause prostate biopsy

Additional relevant MeSH terms:
Dutasteride
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014