Clinical trial NCT00438464: Finasteride in Treating Patients With Stage II Prostate Cancer Who Are Undergoing Surgery
Official title: A Randomized Controlled Trial Evaluating the Tissue Effects of Preoperative Finasteride Versus Placebo for Patients With Clinically Organ-Confined Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Prostate
Stage II Prostate Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: M.D. Anderson Cancer Center
First posted: 2007-02-22
Enrollment: 204
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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)

Primary outcomes:
measure: Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy
timeFrame: At prostatectomy following maximum 6 week treatment period
measure: Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy
timeFrame: At prostatectomy following maximum 6 week treatment period
measure: Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 3 (GG3) Biomarker Subgroups at Prostatectomy
timeFrame: At prostatectomy following maximum 6 week treatment period.
measure: Comparison of Biomarkers Between Treatment Arms: Percentage Change of Tumor Cells Exhibiting Detectable Staining Within Gleason Grade 4 (GG4) Biomarker Subgroup at Prostatectomy
timeFrame: At prostatectomy following maximum 6 week treatment period.
Secondary outcomes:
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Score
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Primary)
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Grade -- Specimen (Secondary)
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor, Node, Metastasis (TNM) Stage
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Margin of Resection (MOR)
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Lymph Node Status
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Cancer Foci
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin of Tumor Foci Per Radical Prostatectomy Specimen (RPS)
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Zonal Origin -- Dominant Tumor Focus
timeFrame: Assessment following maximum 6 week treatment period and prostatectomy
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Gleason Upgrade Between Biopsy and Prostatectomy
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Pathologic Characteristics of Radical Prostatectomy Specimens After Treatment: Tumor Volume (Cubic Centimeter)
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Characteristics of Blood Biomarkers: Prostate-specific Antigen (ng/mL) Percentage Change (%)
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Characteristics of Blood Biomarkers: Testosterone (ng/dL) Percentage Change
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Characteristics of Blood Biomarkers: Dihydrotestosterone (ng/dL) Percentage Change
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Characteristics of Blood Biomarkers: Estrone (ng/dL) Percentage Change
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Characteristics of Blood Biomarkers: Estradiol (ng/dL) Percentage Change
timeFrame: Baseline biopsy to prostatectomy following maximum 6 week treatment period
measure: Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups (Mean)
timeFrame: At prostatectomy following maximum 6 week treatment period
measure: Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Placebo Treatment Arm for Biomarker Subgroups (Mean)
timeFrame: At prostatectomy following maximum 6 week treatment period.
measure: Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Exhibiting Detectable Staining Within Finasteride Treatment Arm for Biomarker Subgroups
timeFrame: At prostatectomy following maximum 6 week treatment period
measure: Comparison of Biomarkers Between Gleason Grades GG3 & GG4: Percentage of Tumor Cells Within Placebo Treatment Arm for Biomarker Subgroups
timeFrame: At prostatectomy following maximum 6 week treatment period.
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Audie L Murphy Veterans Affairs Hospital
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
city: San Antonio
country: United States
facility: University Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jeri Kim
role: PRINCIPAL_INVESTIGATOR
References: