Finasteride and Flutamide in Pre-surgical Trial in Prostate Cancer.

Phase 2

Completed

• Conditions: Prostate Cancer; Prostatic Intraepithelial Neoplasia
• Interventions: Drug: Flutamide; Drug: Finasteride; Other: Placebo

• Registration Number: NCT06601205
• Lead Sponsor: Ente Ospedaliero Ospedali Galliera

Brief Summary

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.

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 Timeline

• Study Start: 2004-01-01
• Primary Completion: 2008-03-20
• Study Completion: 2017-06-16
• Status Verified: 2019-02
• Study First Submitted: 2019-02-12
• Study First Submitted QC: 2024-09-13
• Last Update Submitted: 2024-09-13
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 125

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Flutamide	Flutamide	1 tablet 250 mg daily until the day before surgery
Finasteride	Finasteride	1 tablet 5 mg daily until the day before surgery
Placebo	Placebo	1 tablet daily until the day before surgery

Primary Outcome Measures

Name	Time	Method
Change of Nuclear area size	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.

Secondary Outcome Measures

Name	Time	Method
Change of ki-67 value	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.
Change Kariometry value	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.
Serum biomarkers values	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.
Adverse Events	4-6 weeks (during the treatment)	Toxicity is assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3, 2003).
Recurrence-free survival	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.
Comparison of Event free survival	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.
Comparison of Overall Survival	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.

Trial Locations

Locations (1)

Medical Oncology Ente Ospedaliero Ospedali Galliera; 🇮🇹 Genova, Italy