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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00438464
• Collaborator: M.D. Anderson Cancer Center (Other)
• Enrollment: 204
• Locations: 8
• Arms: 2
• Duration (Months): 62
• Patients Per Site: 25.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Stage II Prostate Cancer	Drug: Finasteride; Other: Placebo; Procedure: Prostatectomy; Other: Laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

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

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

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

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

5. 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 Design

• Study Type: Interventional
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial Evaluating the Tissue Effects of Preoperative Finasteride Versus Placebo for Patients With Clinically Organ-Confined Prostate Cancer
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy [At prostatectomy following maximum 6 week treatment period]

   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.

2. Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy [At prostatectomy following maximum 6 week treatment period]

   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.

3. Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy [At prostatectomy following maximum 6 week treatment period.]

   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.

4. Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy [At prostatectomy following maximum 6 week treatment period.]

   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.

Secondary Outcome Measures

1. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Score [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

2. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Primary) [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

3. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Secondary) [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

4. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor, Node, Metastasis (TNM) Stage [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

5. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Margin of Resection (MOR) [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

6. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Lymph Node Status [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

7. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Cancer Foci [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

8. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin of Tumor Foci Per Radical Prostatectomy Specimen (RPS) [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

9. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin -- Dominant Tumor Focus [Assessment following maximum 6 week treatment period and prostatectomy]

   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.

10. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Upgrade Between Biopsy and Prostatectomy [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    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.

11. Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor Volume (Cubic Centimeter) [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    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.

12. Characteristics of Blood Biomarkers: Prostate-specific Antigen (ng/mL) Percentage Change (%) [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    Characteristics of blood biomarkers using pretreatment and posttreatment values. Prostate-specific antigen (PSA) blood test measuring protein produced by prostate cells.

13. Characteristics of Blood Biomarkers: Testosterone (ng/dL) Percentage Change [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood tests used for measuring the amount of testosterone in the blood.

14. Characteristics of Blood Biomarkers: Dihydrotestosterone (ng/dL) Percentage Change [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    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.

15. Characteristics of Blood Biomarkers: Estrone (ng/dL) Percentage Change [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    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.

16. Characteristics of Blood Biomarkers: Estradiol (ng/dL) Percentage Change [Baseline biopsy to prostatectomy following maximum 6 week treatment period]

    Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood test used to measure Estradiol.

17. Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups (Mean) [At prostatectomy following maximum 6 week treatment period]

    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.

18. Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Placebo Treatment Arm for Biomarker Subgroups (Mean) [At prostatectomy following maximum 6 week treatment period.]

    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.

19. Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups [At prostatectomy following maximum 6 week treatment period]

    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.

20. Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Within Placebo Treatment Arm for Biomarker Subgroups [At prostatectomy following maximum 6 week treatment period.]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
2	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195
3	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
4	M D Anderson Cancer Center	Houston	Texas	United States	77030
5	Audie L Murphy Veterans Affairs Hospital	San Antonio	Texas	United States	78209
6	Cancer Therapy and Research Center	San Antonio	Texas	United States	78229
7	University Hospital	San Antonio	Texas	United States	78229
8	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• National Cancer Institute (NCI)
• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Jeri Kim, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00438464
• Other Study ID Numbers: NCI-2009-00856; NCI-2009-00856; CDR0000653463; 2006-0614; MDA03-1-03; N01CN35159; P30CA016672
• First Posted: Feb 22, 2007
• Last Update Posted: Mar 9, 2016
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Prostatic Neoplasms; Finasteride

Study Results

Participant Flow

Recruitment Details	Recruitment period: From 2007 to 2012 recruitment was done at various medical clinic locations.
Pre-assignment Detail	Of the 210 participants recruited, 204 were randomized to the study.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Period Title: Overall Study
STARTED	103	101
Received Assigned Intervention	89	94
COMPLETED	89	94
NOT COMPLETED	14	7

Baseline Characteristics

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)	Total
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.	Total of all reporting groups
Overall Participants	89	94	183
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	62	60
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	89 100%	94 100%	183 100%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 1.1%	0 0%	1 0.5%
Black	5 5.6%	7 7.4%	12 6.6%
Hispanic	5 5.6%	2 2.1%	7 3.8%
White	78 87.6%	85 90.4%	163 89.1%
Region of Enrollment (participants) [Number]
United States	89 100%	94 100%	183 100%

Outcome Measures

1. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Score
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants. One participant in each arm was excluded due to hormonal therapy effect resulting in lack of assignment of Gleason Grade.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	88	93
Gleason Score 6	12 13.5%	10 10.6%
Gleason Score 7	71 79.8%	78 83%
Gleason Score 8	2 2.2%	1 1.1%
Gleason Score 9	3 3.4%	4 4.3%

2. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Primary)
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants. One participant in each arm was excluded due to hormonal therapy effect resulting in lack of assignment of Gleason Grade.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	88	93
Grade 3	65 73%	75 79.8%
Grade 4	23 25.8%	18 19.1%

3. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Secondary)
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants. One participant in each arm was excluded due to hormonal therapy effect resulting in lack of assignment of Gleason Grade.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	88	93
Grade 3	31 34.8%	24 25.5%
Grade 4	53 59.6%	64 68.1%
Grade 5	4 4.5%	5 5.3%

4. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor, Node, Metastasis (TNM) Stage
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

All evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
pT2	73 82%	74 78.7%
pT3a	11 12.4%	15 16%
pT3b	5 5.6%	5 5.3%

5. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Margin of Resection (MOR)
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
Positive	17 19.1%	16 17%
Negative	67 75.3%	76 80.9%
Equivocal	5 5.6%	2 2.1%

6. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Lymph Node Status
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
PN0	46 51.7%	43 45.7%
PN1	2 2.2%	2 2.1%
pNX	41 46.1%	49 52.1%

7. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Cancer Foci
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
1 Focus	15 16.9%	11 11.7%
2 Foci	18 20.2%	20 21.3%
3 Foci	28 31.5%	28 29.8%
4 Foci	13 14.6%	20 21.3%
>/= 5 Foci	15 16.9%	15 16%

8. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin of Tumor Foci Per Radical Prostatectomy Specimen (RPS)
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
PZ	35 39.3%	38 40.4%
PZ + TZ	49 55.1%	50 53.2%
PZ + TZ + CZ	2 2.2%	2 2.1%
PZ + CZ	0 0%	1 1.1%
TZ	3 3.4%	3 3.2%

9. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin -- Dominant Tumor Focus
Description	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.
Time Frame	Assessment following maximum 6 week treatment period and prostatectomy

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
PZ	67 75.3%	73 77.7%
TZ	22 24.7%	21 22.3%

10. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Upgrade Between Biopsy and Prostatectomy
Description	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.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
No	63 70.8%	70 74.5%
Yes	26 29.2%	24 25.5%

11. Secondary Outcome

Title	Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor Volume (Cubic Centimeter)
Description	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.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	89	94
Total	1.0	0.8
PZ Cancer focus/foci	0.6	0.5
TZ cancer focus/foci	0.0	0.0

12. Secondary Outcome

Title	Characteristics of Blood Biomarkers: Prostate-specific Antigen (ng/mL) Percentage Change (%)
Description	Characteristics of blood biomarkers using pretreatment and posttreatment values. Prostate-specific antigen (PSA) blood test measuring protein produced by prostate cells.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	75	80
Median (Full Range) [percentage of change]	-39.4	-4.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Characteristics of Blood Biomarkers: Testosterone (ng/dL) Percentage Change
Description	Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood tests used for measuring the amount of testosterone in the blood.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	76	80
Median (Full Range) [percentage of change]	13	-4.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Characteristics of Blood Biomarkers: Dihydrotestosterone (ng/dL) Percentage Change
Description	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.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	74	79
Median (Full Range) [percentage of change]	-64.8	-3.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	Characteristics of Blood Biomarkers: Estrone (ng/dL) Percentage Change
Description	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.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	75	79
Median (Full Range) [percentage of change]	-8.9	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.805
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Secondary Outcome

Title	Characteristics of Blood Biomarkers: Estradiol (ng/dL) Percentage Change
Description	Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood test used to measure Estradiol.
Time Frame	Baseline biopsy to prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Analysis includes all evaluable participants.

Arm/Group Title	Arm I (Finasteride)	Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	76	79
Median (Full Range) [percentage of change]	7.2	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

17. Primary Outcome

Title	Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Of total 183 enrolled participants in both arms, 62 Finasteride and 68 Placebo participants respectively had a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	Finasteride Arm Within GG3	Placebo Arm Within GG3
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	62	68
VEGF (N=37,55)	80	90
ERβ (N=35, 55)	15.0	6.6
AR (N=35, 54)	75.2	78.3
Ki-67 (N=37,54)	1.1	1.3
SRD5A2 (N=45,47)	100	90
UBE2C (N=34,55)	0.4	0.3
Caspase (N=38,55)	0.2	0.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	VEGF3, Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Estrogen receptor beta (ERβ), Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Androgen receptor (AR), Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Ki-67 protein, Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	3-oxo-5α-steroid 4-dehydrogenase 2 (SRD5A2), Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Ubiquitin-conjugating enzyme E2C (UBE2C), Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Cleaved Caspase 3 (Caspase), Within GG3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

18. Primary Outcome

Title	Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Of total 183 enrolled participants in both arms, 62 Finasteride and 68 Placebo participants respectively had a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	Finasteride Arm Within GG4	Placebo Arm Within GG4
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	62	68
VEGF (N=48,61)	85	70
ERβ (N=48,62)	8.0	9.5
AR (N=48,62)	63.71	75.9
Ki-67 (N=48,62)	1.3	1.4
SRD5A2 (N=38,69)	95	90
UBE2C (N=46,62)	0.3	0.3
Caspase (N=47,61)	0.06	0.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Vascular Epithelial Growth Factor (VEGF3), Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Estrogen receptor beta (ERβ), Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Androgen receptor (AR), Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Ki-67 protein, Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	3-oxo-5α-steroid 4-dehydrogenase 2 (SRD5A2), Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	UBE2C, Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Caspase, Within GG4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

19. Primary Outcome

Title	Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period.

Outcome Measure Data

Analysis Population Description

Of total 183 enrolled participants in both arms, 62 Finasteride and 68 Placebo participants respectively had a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	Finasteride Arm Within GG3	Placebo Arm Within GG3
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	62	68
VEGF (N=37,55)	63.9 (36.3)	63.7 (38)
ERβ (N=35, 55)	18.1 (15.6)	14.8 (14.7)
AR (N=35, 54)	69.8 (17.3)	72.4 (16.7)
Ki-67 (N=37,54)	1.6 (1.4)	1.5 (1.0)
SRD5A2 (N=45,47)	72.9 (37.0)	64.7 (43.7)
UBE2C (N=34,55)	0.5 (0.4)	0.5 (0.5)
Caspase (N=38,55)	0.4 (0.7)	0.2 (0.2)

20. Primary Outcome

Title	Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period.

Outcome Measure Data

Analysis Population Description

Of total 183 enrolled participants in both arms, 62 Finasteride and 68 Placebo participants respectively had a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	Finasteride Arm Within GG4	Placebo Arm Within GG4
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.	Placebo once daily for 4-6 weeks, then undergo prostatectomy.
Measure Participants	62	68
VEGF (N=48,61)	63.6 (35.5)	59.8 (35.4)
ERβ (N=48,62)	15.0 (15.1)	16.7 (18.8)
AR (N=48,62)	64.3 (16.67)	68.6 (23.1)
Ki-67 (N=48,62)	1.8 (1.6)	1.7 (1.4)
SRD5A2 (N=38,69)	71.8 (37.6)	64.9 (40.8)
UBE2C (N=46,62)	0.5 (0.4)	0.5 (0.4)
Caspase (N=47,61)	0.1 (0.1)	0.06 (0.08)

21. Secondary Outcome

Title	Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups (Mean)
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Of total 89 enrolled participants in the Finasteride Arm, 62 participants had either a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	GG3, Within Finasteride Arm	GG4, Within Finasteride Arm
Arm/Group Description	Participants with GG3 score receiving 5 mg daily for 4-6 weeks, then receive prostatectomy.	Participants with GG4 score receiving 5 mg daily for 4-6 weeks, then receive prostatectomy.
Measure Participants	62	62
VEGF (N=37,48)	63.9 (36.3)	63.7 (35.5)
ERβ (N=35,48)	18.1 (15.6)	15.0 (15.1)
AR (N=35,48)	69.8 (17.3)	64.3 (16.7)
Ki-67 (N=37,48)	1.6 (1.4)	1.8 (1.6)
SRD5A2 (N=45,38)	72.9 (37.0)	71.8 (37.6)
UBE2C (N=34,46)	0.5 (0.4)	0.5 (0.4)
Caspase (N=38,47)	0.4 (0.7)	0.1 (0.1)

22. Secondary Outcome

Title	Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Placebo Treatment Arm for Biomarker Subgroups (Mean)
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period.

Outcome Measure Data

Analysis Population Description

Of total 94 enrolled participants in the Placebo Arm, 68 participants had either a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	GG3, Within Placebo Arm	GG4, Within Placebo Arm
Arm/Group Description	Participants with GG3 score in Placebo Arm, receiving placebo daily for 4-6 weeks, then receive prostatectomy.	Participants with GG4 score in Plaebo Arm, receiving placebo daily for 4-6 weeks, then receive prostatectomy.
Measure Participants	68	68
VEGF (N=55,61)	63.7 (38)	59.7 (35.4)
ERβ (N=55,62)	14.8 (14.7)	16.7 (18.8)
AR (N=54,62)	72.4 (16.7)	68.6 (23.1)
Ki-67 (N=54,62)	1.5 (1.0)	1.7 (1.4)
SRD5A2 (N=47,69)	64.7 (43.7)	64.9 (40.8)
UBE2C (N=55,62)	0.5 (0.5)	0.5 (0.4)
Caspase (N=55,61)	0.2 (0.2)	0.06 (0.08)

23. Secondary Outcome

Title	Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period

Outcome Measure Data

Analysis Population Description

Of total 89 enrolled participants in the Finasteride Arm, 62 participants had either a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	Within GG3, Finasteride Arm	Within GG4, Finasteride Arm
Arm/Group Description	Participants with GG3 score in Finasteride Arm, receiving 5 mg daily for 4-6 weeks, then receive prostatectomy.	Participants with GG4 score in Finasteride Arm, receiving 5 mg daily for 4-6 weeks, then receive prostatectomy.
Measure Participants	62	62
VEGF (N=37,48)	80	85
ERβ (N=35,48)	15.0	8.0
AR (N=35,48)	75.2	63.7
Ki-67 (N=37,48)	1.1	1.3
SRD5A2 (N=45,38)	100	95
UBE2C (N=34,46)	0.4	0.3
Caspase (N=38,47)	0.2	0.06

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	VEGF3, Within Finasteride Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	ERβ, Within Finasteride Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	AR, Within Finasteride
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Ki-67 protein, Within Finasteride Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	SRD5A2, Within Finasteride Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	UBE2C, Within Finasteride Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Caspase, Within Finasteride Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

24. Secondary Outcome

Title	Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Within Placebo Treatment Arm for Biomarker Subgroups
Description	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.
Time Frame	At prostatectomy following maximum 6 week treatment period.

Outcome Measure Data

Analysis Population Description

Of total 94 enrolled participants in the Placebo Arm, 68 participants had either a qualifying tumor specimen with GG3 or GG4. Differences in number (N) of tissue specimens (tumor foci) is based on feasibility of subgroup participants' radical prostatectomy samples analyzed.

Arm/Group Title	Within GG3, Placebo Arm	Within GG4, Placebo Arm
Arm/Group Description	Participants with GG3 score in Placebo Arm, receiving placebo daily for 4-6 weeks, then receive prostatectomy.	Participants with GG4 score in Plaebo Arm, receiving placebo daily for 4-6 weeks, then receive prostatectomy.
Measure Participants	68	68
VEGF (N=55,61)	90	70
ERβ (N=55,62)	6.6	9.5
AR (N=54,62)	78.3	75.9
Ki-67 (N=54,62)	1.3	1.4
SRD5A2 (N=47,69)	90	90
UBE2C (N=55,62)	0.3	0.3
Caspase (N=55,61)	0.08	0.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	VEGF3, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	ERβ, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	AR, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Ki-67 protein, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	SRD5A2, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	UBE2C, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm I (Finasteride), Arm II (Placebo)
	Comments	Caspase, Within Placebo Arm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	The final collection of adverse events obtained at the completion of the 4-6 week course of study medication/placebo, before prostatectomy. Overall study period: March 2007 to April 2012.
Arm/Group Title	Arm I (Finasteride)		Arm II (Placebo)
Arm/Group Description	Finasteride 5 mg once daily for 4-6 weeks, then undergo prostatectomy.		Placebo once daily for 4-6 weeks, then undergo prostatectomy.
All Cause Mortality
	Arm I (Finasteride)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Finasteride)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/89 (0%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Finasteride)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/89 (0%)		0/94 (0%)

Limitations/Caveats

Predefined molecular signature could not easily distinguish GG 4 from GG 3 tumor areas in the placebo arm.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.