Finasteride and Flutamide in Pre-surgical Trial in Prostate Cancer. (2F)

September 13, 2024 updated by: Andrea DeCensi, Ente Ospedaliero Ospedali Galliera

A Randomized, Phase IIB, Double Blind, Placebo Controlled, Multicenter, Pre-surgical, Window-of-opportunity Trial of Finasteride Vs. Low-dose Flutamide Vs. Placebo in Prostate Cancer (2F Trial)

Pre-surgical, window-of-opportunity trials provide a suitable model to assess the activity of preventive interventions in a cost-effective manner using tissue biomarkers as surrogate endpoints. Finasteride has been shown to reduce prostate cancer development in a large phase III trial, and flutamide has a well-known anticancer effect in advanced prostate cancer at the dose of 750 mg/day.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this randomized, phase IIB, double blind, placebo controlled, multicenter, pre-surgical, window-of-opportunity trial we compared the effects of finasteride (5 mg/day) versus low-dose flutamide (250 mg/day) or placebo on tissue biomarkers in patients with prostate cancer who were candidate to radical surgery. Specifically, the effects of both drugs on the change in epithelial cell nuclear area in prostate cancer tissue between pre- and post-treatment biopsies was evaluated (primary endpoint). Moreover, the changes of the proliferation marker Ki-67 and of karyometric parameters in benign, dysplastic (HG-PIN) and malignant tissues were evaluated (secondary endpoints). Additional endpoints include the changes of serum PSA and testosterone, assessment of toxicity, overall survival, recurrence-free survival and event-free (recurrence + death) survival. Patients with intracapsular biopsy proven prostate cancer were randomized to either flutamide, 250 mg/day, or finasteride, 5 mg/day, or placebo for 4-6 weeks before radical prostatectomy. Blood samples were taken before and after treatment. At surgery, end-of-study ex-vivo biopsies were obtained from the prostatectomy specimens to assess the treatment changes in nuclear area (primary endpoint), Ki-67, topoisomerase-II-α and a 20-feature karyometric discrimant function in normal, high-grade PIN and malignant tissue. After surgery patients were followed up for at least 15 years to assess recurrence and/or mortality. We also plan to follow-up patients by telephone interview to assess their vital status for up to 20 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
125

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Genova, Italy, 16128
        • Medical Oncology Ente Ospedaliero Ospedali Galliera

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged > 18 years
  • Patients with a biopsy proven, clinically intracapsular PCa who are candidates to radical retropubic prostatectomy
  • ECOG performance status ≤ 2

  • Satisfactory hematological and biochemical functions:

    • Platelets ≥100 x 10^9/L
    • AST and ALT in the normal range
  • Able to understand and sign an informed consent

Exclusion Criteria:

  • Previous hormone treatment during the 8 weeks before enrollment
  • Neurologic and psychiatric diseases precluding patient participation in the study
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing or participating in the study and/or comply with the study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Flutamide
1 tablet 250 mg daily until the day before surgery
Drug: Flutamide
1 tablet daily until the day before surgery
Other Names:
  • Arm A
Experimental: Finasteride
1 tablet 5 mg daily until the day before surgery
Drug: Finasteride
1 tablet daily until the day before surgery
Other Names:
  • Arm B
Placebo Comparator: Placebo
1 tablet daily until the day before surgery
Other: Placebo
1 tablet daily until the day before surgery
Other Names:
  • Arm C

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of Nuclear area size
Time Frame: 4-6 weeks (baseline and at the end of the study biopsy)
The study primary endpoint is the change of epithelial cell nuclear area in prostate cancer tissue and HG-PIN tissue between pre- and post-treatment measure in the two active treatment arms (Finasteride or Flutamide) compared with the placebo arm.
4-6 weeks (baseline and at the end of the study biopsy)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of ki-67 value
Time Frame: 4-6 weeks (baseline and at the end of the study biopsy)
Changes of Ki-67 labeling index in normal, HG-PIN and prostate cancer cells in the three arms.
4-6 weeks (baseline and at the end of the study biopsy)
Change Kariometry value
Time Frame: 4-6 weeks (baseline and at the end of the study biopsy)
Changes in karyometric features in normal HG-PIN and prostate cancer cells in the three arms.
4-6 weeks (baseline and at the end of the study biopsy)
Serum biomarkers values
Time Frame: 4-6 weeks (on blood samples at baseline and the day before surgery)
Changes in total PSA, free PSA and testosterone concentrations after treatment in the three arms.
4-6 weeks (on blood samples at baseline and the day before surgery)
Adverse Events
Time Frame: 4-6 weeks (during the treatment)
Toxicity is assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3, 2003).
4-6 weeks (during the treatment)
Recurrence-free survival
Time Frame: up to 20 years
Comparison of Recurrence-free survival among arms will be assessed by the Kaplan Meier actuarial survival curves and analyzed by the log-rank test and the Cox proportional hazard model for multivariate analyses. Vital status and medical condition will be assessed by telephone interview and clinical visit.
up to 20 years
Comparison of Event free survival
Time Frame: up to 20 years
Comparison of Event free survival among arms will be assessed by the Kaplan Meier actuarial survival curves and analyzed by the log-rank test and the Cox proportional hazard model for multivariate analyses. Vital status and medical condition will be assessed by telephone interview and clinical visit.
up to 20 years
Comparison of Overall Survival
Time Frame: up to 20 years
Comparison of Overall Survival among arms will be assessed by the Kaplan Meier actuarial survival curves and analyzed by the log-rank test and the Cox proportional hazard model for multivariate analyses. Vital status and medical condition will be assessed by telephone interview and clinical visit.
up to 20 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ente Ospedaliero Ospedali Galliera

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Arizona
Università Politecnica delle Marche
Universita degli Studi di Genova
European Institute of Oncology
Cliniche Humanitas Gavazzeni

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrea De Censi, MD, E.O. Ospedali Galliera

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 20, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 16, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 12, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2024

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 19, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13CE20102003
  • Italian League against Cancer (Other Identifier: LILT (Lega Italiana contro i Tumori))
  • Berlucchi Foundation (Other Identifier: Fondazione Berlucchi)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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