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

This study has been completed.
Sponsor:
Collaborator:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00438464
First received: February 20, 2007
Last updated: February 10, 2016
Last verified: June 2015
  Purpose
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 Intervention Phase
Adenocarcinoma of the Prostate
Stage II Prostate Cancer
Drug: Finasteride
Other: Placebo
Procedure: Prostatectomy
Other: Laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy [ Time Frame: At prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy [ Time Frame: At prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy [ Time Frame: At prostatectomy following maximum 6 week treatment period. ] [ Designated as safety issue: No ]
    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.

  • Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy [ Time Frame: At prostatectomy following maximum 6 week treatment period. ] [ Designated as safety issue: No ]
    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:
  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Score [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Primary) [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Secondary) [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor, Node, Metastasis (TNM) Stage [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Margin of Resection (MOR) [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Lymph Node Status [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Cancer Foci [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin of Tumor Foci Per Radical Prostatectomy Specimen (RPS) [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin -- Dominant Tumor Focus [ Time Frame: Assessment following maximum 6 week treatment period and prostatectomy ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Upgrade Between Biopsy and Prostatectomy [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor Volume (Cubic Centimeter) [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Characteristics of Blood Biomarkers: Prostate-specific Antigen (ng/mL) Percentage Change (%) [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    Characteristics of blood biomarkers using pretreatment and posttreatment values. Prostate-specific antigen (PSA) blood test measuring protein produced by prostate cells.

  • Characteristics of Blood Biomarkers: Testosterone (ng/dL) Percentage Change [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood tests used for measuring the amount of testosterone in the blood.

  • Characteristics of Blood Biomarkers: Dihydrotestosterone (ng/dL) Percentage Change [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Characteristics of Blood Biomarkers: Estrone (ng/dL) Percentage Change [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Characteristics of Blood Biomarkers: Estradiol (ng/dL) Percentage Change [ Time Frame: Baseline biopsy to prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    Characteristics of blood biomarkers using pretreatment and posttreatment values. Blood test used to measure Estradiol.

  • Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups (Mean) [ Time Frame: At prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Placebo Treatment Arm for Biomarker Subgroups (Mean) [ Time Frame: At prostatectomy following maximum 6 week treatment period. ] [ Designated as safety issue: No ]
    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.

  • Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups [ Time Frame: At prostatectomy following maximum 6 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Within Placebo Treatment Arm for Biomarker Subgroups [ Time Frame: At prostatectomy following maximum 6 week treatment period. ] [ Designated as safety issue: No ]
    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.


Enrollment: 204
Study Start Date: February 2007
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: PLCB
Other: Laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438464

Locations
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Audie L Murphy Veterans Affairs Hospital
San Antonio, Texas, United States, 78209
Cancer Therapy and Research 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
Sponsors and Collaborators
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Jeri Kim M.D. Anderson Cancer Center
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00438464     History of Changes
Other Study ID Numbers: NCI-2009-00856  NCI-2009-00856  CDR0000653463  2006-0614  MDA03-1-03  N01CN35159  P30CA016672 
Study First Received: February 20, 2007
Results First Received: October 20, 2015
Last Updated: February 10, 2016
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Finasteride
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Urological Agents

ClinicalTrials.gov processed this record on May 01, 2016