Clinical trial NCT06601205: Finasteride and Flutamide in Pre-surgical Trial in Prostate Cancer.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Prostate Cancer
Prostatic Intraepithelial Neoplasia
Keywords: Prostate Cancer
Prostatic Intraepithelial Neoplasia
Chemoprevention
Flutamide
Finasteride
Biomarkers, drug response
Karyometry
Lead sponsor: Ente Ospedaliero Ospedali Galliera
Sponsor class: OTHER
Collaborators: name: Universita degli Studi di Genova
name: Cliniche Humanitas Gavazzeni
name: Università Politecnica delle Marche
name: European Institute of Oncology
name: University of Arizona
First posted: 2024-09-19
Enrollment: 125
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study was a prospective, randomized, phase IIB, placebo controlled, double-blind, pre-surgical trial of Finasteride 5 mg day versus Flutamide 250 mg day versus placebo in men with PCa. Patients with a biopsy proven, clinically intracapsular prostate cancer who were candidate to radical retropubic prostatectomy were enrolled in four different institutions in Northern Italy. Different biopsy criteria according to each contributing centre were acceptable provided that a minimum of 8 cores were evaluable. Patients were randomized to receive either flutamide, 250 mg/day orally, or finasteride, 5 mg/day orally, or oral placebo in a double-blind manner beginning 4 to 6 weeks before surgery.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of Nuclear area size
timeFrame: 4-6 weeks (baseline and at the end of the study biopsy)
Secondary outcomes:
measure: Change of ki-67 value
timeFrame: 4-6 weeks (baseline and at the end of the study biopsy)
measure: Change Kariometry value
timeFrame: 4-6 weeks (baseline and at the end of the study biopsy)
measure: Serum biomarkers values
timeFrame: 4-6 weeks (on blood samples at baseline and the day before surgery)
measure: Adverse Events
timeFrame: 4-6 weeks (during the treatment)
measure: Recurrence-free survival
timeFrame: up to 20 years
measure: Comparison of Event free survival
timeFrame: up to 20 years
measure: Comparison of Overall Survival
timeFrame: up to 20 years
Other outcomes:
Locations:
city: Genova
country: Italy
facility: Medical Oncology Ente Ospedaliero Ospedali Galliera
Study officials:
affiliation: E.O. Ospedali Galliera
name: Andrea De Censi, MD
role: PRINCIPAL_INVESTIGATOR
References: