Finasteride in Treating Patients With Stage II Prostate Cancer Who Are Undergoing Surgery

A Randomized Controlled Trial Evaluating the Tissue Effects of Preoperative Finasteride Versus Placebo for Patients With Clinically Organ-Confined Prostate Cancer

This randomized phase II trial studies how well finasteride works in treating patients with stage II prostate cancer who are undergoing surgery. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using finasteride may fight prostate cancer by lowering the amount of testosterone the body makes. Giving finasteride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Study Overview

• Status: Completed
• Conditions: Stage II Prostate Cancer; Adenocarcinoma of the Prostate
• Intervention / Treatment: Other: Placebo; Other: Laboratory biomarker analysis; Drug: Finasteride; Procedure: Prostatectomy

Detailed Description

PRIMARY OBJECTIVES:

I. Compare the frequency of discriminating molecular marker expression in Gleason grade (GG) 3 cores, adjusted for Gleason score (GS) at prostatectomy, in patients with stage II prostate cancer treated with neoadjuvant finasteride vs placebo.

SECONDARY OBJECTIVES:

I. Compare the frequency with which grade 3 and grade 4 tumors occur in these patients.

II. Determine the frequency of discriminating molecular signature expression in tissue microarray cores segregated by GS at prostatectomy in these patients.

III. Compare GG 3-appearing areas (in tumors rated GS 6 at prostatectomy) in patients treated with finasteride vs placebo.

IV. Compare GG 3-appearing areas (in tumors rated GS 7 at prostatectomy) in patients treated with finasteride vs placebo.

V. Compare GG 4-appearing areas (in tumors rated GS 7 at prostatectomy) in patients treated with finasteride vs placebo.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study.

Patients are stratified according to study site, Gleason score (6 vs 7), and type of prostatectomy (open vs robotic/laparoscopic). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive finasteride orally (PO) once daily (QD) for 4-6 weeks, and then undergo prostatectomy.

Arm II: Patients receive placebo PO QD for 4-6 weeks, and then undergo prostatectomy.

Tumor tissue obtained at prostatectomy is used to make tissue microarrays and is analyzed by immunohistochemistry for molecular marker expression studies.

After completion of study treatment, patients are followed up for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • University Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
    • San Antonio, Texas, United States, 78209
      • Audie L Murphy Veterans Affairs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Criteria:

• Histologically confirmed adenocarcinoma of the prostate
• Clinical stage T1c or T2 (stage II)
• Gleason score of 6 or 7 on initial biopsy
• Prostate-specific antigen (PSA) level less than 10 ng/mL within the past 3 months
• Candidate for and scheduled to undergo prostatectomy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 70-100%
• Fertile patients must use effective contraception
• No active malignancy at any other site
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to finasteride
• No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection; Symptomatic congestive heart failure; Unstable angina pectoris; Cardiac arrhythmia
• No psychiatric illness or social situation that would preclude study compliance
• More than 6 months since prior hormonal agents, including dutasteride or finasteride
• More than 6 months since prior chemotherapy
• More than 1 month since prior participation in another investigational study
• No prior radiotherapy for the primary tumor
• No concurrent dehydroepiandrosterone, phytoestrogen supplements, antiandrogen therapy, dutasteride, or other finasteride
• No concurrent anticoagulation, except for the use of daily acetylsalicylic acid (81 mg to 325 mg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (Finasteride); Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Other: Laboratory biomarker analysis; Correlative studies; Drug: Finasteride; Given PO; Other Names: Proscar; Finastid; MK 906; Prostide; Procedure: Prostatectomy; Undergo prostatectomy; Other Names: Radical Prostatectomy; Therapeutic conventional surgery; Simple Prostatectomy
Placebo Comparator: Arm II (Placebo); Placebo once daily for 4-6 weeks, then undergo prostatectomy.	Other: Placebo; Given PO; Other Names: PLCB; Other: Laboratory biomarker analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy	Molecular marker expression based on tissue microarray (TMA) derived from dominant tumor focus. Staining microarrays for high-throughput assessment of candidate gene expression and data modeling constructed with a tissue microarray apparatus and 0.6-mm biopsy cores, representative of tumor grades and scores (Gleason Grades 3 (GG3) and Gleason Grade 4 (GG4)). The percentage of tumor cells exhibiting detectable staining, scored as 0 to 10 where higher score designates more involvement, as applicable for: vascular epithelial growth factor (VEFG), estrogen receptor beta (ERβ), androgen receptor (AR), 3-oxo-5α-steroid 4-dehydrogenase 2 (SRD5A2), ubiquitin-conjugating enzyme E2C (UBE2C), and Cleaved Caspase 3 (Caspase). P values are based on non-parametric Wilcoxon rank-sum test.	At prostatectomy following maximum 6 week treatment period
Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy	Biomarkers using pretreatment and posttreatment values. Staining microarrays for high-throughput assessment of candidate gene expression and data modeling constructed with a tissue microarray apparatus and 0.6-mm biopsy cores, representative of tumor grades and scores (Gleason Grades 3 (GG3) and Gleason Grade 4 (GG4)). The percentage of tumor cells exhibiting detectable staining, scored as 0 to 10 where higher score designates more involvement, as applicable for: VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C. P values are based on non-parametric Wilcoxon rank-sum test.	At prostatectomy following maximum 6 week treatment period
Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy	Molecular marker expression compared between tumor foci using Biomarkers pretreatment and posttreatment values. Staining microarrays for high-throughput assessment of candidate gene expression and data modeling constructed with a tissue microarray apparatus and 0.6-mm biopsy cores, representative of tumor grades and scores (Gleason Grades 3 (GG3) and Gleason Grade 4 (GG4)). The percentage of tumor cells exhibiting detectable staining, scored as 0 to 10 where higher score designates more involvement, as applicable for: VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C.	At prostatectomy following maximum 6 week treatment period.
Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy	Molecular marker expression compared between tumor foci using biomarkers pretreatment and posttreatment values. Staining microarrays for high-throughput assessment of candidate gene expression and data modeling constructed with a tissue microarray apparatus and 0.6-mm biopsy cores, representative of tumor grades and scores (Gleason Grades 3 (GG3) and Gleason Grade 4 (GG4)). The percentage of tumor cells exhibiting detectable staining, scored as 0 to 10 where higher score designates more involvement, as applicable for: VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C.	At prostatectomy following maximum 6 week treatment period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Score	Frequency of Grade 3 and Grade 4 tumors in two treatment groups: Participants consist of men with adenocarcinoma of prostate, clinical stage T1c or T2, with Gleason score of 6 or 7 and PSA level < 10 ng/mL, who are scheduled to undergo prostatectomy. 2005 International Society of Urological Pathologists recommendations for Gleason scoring (GS) used to grade tumors based upon its microscopic appearance: a primary grade is assigned to most common tumor pattern, and a second grade to next most common tumor pattern. Gleason score (GS) is sum of the two Gleason grades, based on scale of 2-10 with lowest numbers indicating slow-growing tumor unlikely to spread and highest numbers indicating an aggressive tumor. Gleason grade = 1-5; Gleason score = 2-10; 5 and 10 indicate worst prognosis. American Joint Committee on Cancer (AJCC) staging describes extent of disease progression utilizing TNM scoring system: Tumor size, Lymph Nodes affected, Metastases. Higher stage cancers are more advanced.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Primary)	Frequency of Grade 3 and Grade 4 tumors in two treatment groups: Participants consist of men with adenocarcinoma of the prostate, clinical stage T1c or T2, with a Gleason score of 6 or 7 and a PSA level < 10 ng/mL, who are scheduled to undergo prostatectomy.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Secondary)	Frequency of Grade 3, Grade 4 and Grade 5 tumors in two treatment groups: Participants will consist of men with adenocarcinoma of the prostate, clinical stage T1c or T2, with a Gleason score of 6 or 7 and a PSA level < 10 ng/mL, who are scheduled to undergo prostatectomy.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor, Node, Metastasis (TNM) Stage	American Joint Committee on Cancer (AJCC) system 6th edition (2002) describing amount and spread of cancer body, using TNM. T describes the size of the tumor and any spread of cancer into nearby tissue; N describes spread of cancer to nearby lymph nodes; and M describes metastasis (spread of cancer to other parts of the body). Numbers after the T (such as T1, T2, T3, and T4) describe tumor size and/or amount of spread into nearby structures. The higher the T number, the larger the tumor and/or the more it has grown into nearby tissues where T3a reflects tumor has spread through the capsule on one or both sides; and T3b reflects tumor has invaded one or both seminal vesicles.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Margin of Resection (MOR)	Edge or border of tissue removed in cancer surgery. The margin is described as negative or clean when the pathologist finds no cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. The margin is described as positive or involved when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Lymph Node Status	Status of cancer spread to lymph nodes; PN0 Cancer that has not spread to the lymph nodes. Cancer that has not spread to the lymph nodes. The N category describes whether the cancer has spread into nearby lymph nodes. NX means the nearby lymph nodes cannot be evaluated. N0 means nearby lymph nodes do not contain cancer. Numbers after the N (such as N1, N2, and N3) describe the size, location, and/or the number of nearby lymph nodes affected by cancer. The higher the N number, the greater the cancer spread to nearby lymph nodes.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Cancer Foci	Diagnosis of a small focus of prostatic adenocarcinoma on a prostate needle biopsy from pathologist's identification of an architecturally abnormal focus of epithelial structures at rather low magnification.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin of Tumor Foci Per Radical Prostatectomy Specimen (RPS)	Tumor distribution within zones of the prostate using radical prostatectomy specimen (RPS) where number of foci categorized by zone defined as: PZ, peripheral zone; TZ, transition zone; CZ, central zone.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin -- Dominant Tumor Focus	Dominant tumor focus, distribution within zones of the prostate using radical prostatectomy specimen (RPS) where number of foci categorized by zone defined as: PZ, peripheral zone; TZ, transition zone; CZ, central zone. Dominant tumor focus is the largest, index lesion, single high risk focus of the prostate cancer.	Assessment following maximum 6 week treatment period and prostatectomy
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Upgrade Between Biopsy and Prostatectomy	Change in Gleason Score from biopsy to prostatectomy where an upgrade refers to a higher Gleason Score signifying worsening of tumor. Gleason scoring (GS) to based on microscopic appearance using 2005 International Society of Urological Pathologists recommendation.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor Volume (Cubic Centimeter)	Characteristics of tumor considering total zone cancer volume, and cancer volume using zonal foci categorized as: PZ, peripheral zone; TZ, transition zone; CZ, central zone.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Characteristics of Blood Biomarkers: Prostate-specific Antigen (ng/mL) Percentage Change (%)	Characteristics of blood biomarkers using pretreatment and posttreatment values. Prostate-specific antigen (PSA) blood test measuring protein produced by prostate cells.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Characteristics of Blood Biomarkers: Testosterone (ng/dL) Percentage Change	Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood tests used for measuring the amount of testosterone in the blood.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Characteristics of Blood Biomarkers: Dihydrotestosterone (ng/dL) Percentage Change	Characteristics of blood biomarkers using pretreatment and posttreatment values. Dihydrotestosterone (DHT) blood test measures serum concentrations of dihydrotestosterone and is closely related to those of testosterone.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Characteristics of Blood Biomarkers: Estrone (ng/dL) Percentage Change	Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood test used to measure Estrone (E1), one of the three estrogens, which also includes estriol and estradiol.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Characteristics of Blood Biomarkers: Estradiol (ng/dL) Percentage Change	Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood test used to measure Estradiol.	Baseline biopsy to prostatectomy following maximum 6 week treatment period
Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups (Mean)	Molecular marker expression compared between tumor foci, characteristics of blood biomarkers using pretreatment and posttreatment values. VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C.	At prostatectomy following maximum 6 week treatment period
Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Placebo Treatment Arm for Biomarker Subgroups (Mean)	Molecular marker expression compared between tumor foci, characteristics of blood biomarkers using pretreatment and posttreatment values. VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C.	At prostatectomy following maximum 6 week treatment period.
Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups	Molecular marker expression compared between tumor foci, characteristics of blood biomarkers using pretreatment and posttreatment values. VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C. P values are based on non-parametric Wilcoxon rank-sum test.	At prostatectomy following maximum 6 week treatment period
Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Within Placebo Treatment Arm for Biomarker Subgroups	Molecular marker expression compared between tumor foci, characteristics of blood biomarkers using pretreatment and posttreatment values. VEGF denotes vascular epithelial growth factor, ERβ estrogen receptor beta, AR androgen receptor, SRD5A2, 3-oxo-5α-steroid 4-dehydrogenase 2, UBE2C, ubiquitin-conjugating enzyme E2C. P values are based on non-parametric Wilcoxon rank-sum test.	At prostatectomy following maximum 6 week treatment period.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Jeri Kim, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 20, 2007
• First Submitted That Met QC Criteria: February 20, 2007
• First Posted (Estimate): February 22, 2007

Study Record Updates

• Last Update Posted (Estimate): March 9, 2016
• Last Update Submitted That Met QC Criteria: February 10, 2016
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; 5-alpha Reductase Inhibitors; Finasteride
• Other Study ID Numbers: NCI-2009-00856 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA016672 (U.S. NIH Grant/Contract); N01CN35159 (U.S. NIH Grant/Contract); CDR0000653463; 2006-0614 (Other Identifier: M D Anderson Cancer Center); MDA03-1-03 (Other Identifier: DCP)