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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Adenocarcinoma of the Prostate, Stage II Prostate Cancer

Intervention / Treatment
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* Drug: Finasteride
* Other: Placebo
* Procedure: Prostatectomy
* Other: Laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (Finasteride)<br>Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy. | Drug: Finasteride<br>* Given PO<br>* Other names: Prostide;Procedure: Prostatectomy<br>* Undergo prostatectomy<br>* Other names: Simple Prostatectomy;Other: Laboratory biomarker analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (Placebo)<br>Placebo once daily for 4-6 weeks, then undergo prostatectomy. | Other: Placebo<br>* Given PO<br>* Other names: PLCB;Other: Laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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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. |