Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage III Prostate Cancer, Stage II Prostate Cancer, Stage I Prostate Cancer
Conditions
Brief summary
RATIONALE: Genistein may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This randomized phase II trial is studying how well genistein works in treating patients with prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. Determine whether genistein treatment will decrease the number of circulating prostate cells (CPCs) in the peripheral blood as measured by qRT-PCR for PSA performed on RNA extracted from peripheral blood mononuclear cells (PBMNCs). SECONDARY OBJECTIVES: I. Determine the natural history of circulating prostate cells (CPCs) in a cohort of subjects prior to and post radical prostatectomy. II. Compare the measurement of PSA between three separate methods: in CPCs by qRT-PCR, in serum by the standard clinical chemistry assay (i.e., ELISA), and in plasma and serum by the nano-PSA assay. III. Measure the effect of genistein on gene and protein expression in prostate tissue by qRT-PCR and immunohistochemistry, respectively, for the following genes and their respective protein products: HSP27, MMP-2, ALK-2, BASP1, and HCF2. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. ARM II: Patients receive oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. All patients undergo radical prostatectomy at least 2 weeks, but not more than 3 months following the start of therapy. After completion of study treatment, patients are followed at 1, 6, and 12 months.
Interventions
DIETARY_SUPPLEMENTgenistein
Given orally
OTHERplacebo
Given orally
PROCEDUREtherapeutic conventional surgery
Radical prostatectomy for treatment of prostate cancer
Sponsors
National Cancer Institute (NCI)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion * Participants must have a pathologic diagnosis of prostate cancer within the past 6 months, have clinical stage T1-3 disease, PSA \>= 10, Gleason score \>= 8, and have elected to undergo radical prostatectomy; those found to have detectable circulating prostate cancer cells in the blood as detected by qRT-PCR for PSA will be eligible to proceed onto the treatment phase of the protocol; pathology slides used for diagnosis will be submitted to the SPORE tissue pathology core for review * ECOG performance status 0-1 * Hemoglobin \> 9.0gm/dl * Platelets \>= 100 K/uL * ANC \> 1000/uL * AST (SGOT)/ALT (SGPT) \< 3X upper limit of normal * Creatinine \< 2.0 mg/dl * Total bilirubin \< 2 mg/dl (Note: Subjects with a higher level of bilirubin due to a familial defect in bilirubin metabolism will be considered on an individual basis) * Participants must agree not to take soy supplements * Ability to understand and the willingness to sign a written informed consent document * Willingness to take study agent for at least 2 weeks prior to radical prostatectomy Exclusion * History of venous thrombosis within past year * Participants must not be receiving active therapy for neoplastic disorders (including hormone or radiation therapy for prostate cancer) * Participants may not be receiving any other investigational agents * Known soy intolerance * Medical conditions that, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Circulating Prostate Cells (CPCs) in the Blood as Determined by qRT-PCR for PSA on RNA Extracted From PBMNCs | At screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery | Blood will be collected to analyze the number of CPC's at screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Natural History of Circulating Prostate Cells (CPCs) in a Cohort of Subjects Prior to and Post Radical Prostatectomy | At baseline, 1 and 12 months after surgery | Blood will be drawn to analyze the natural history of circulating prostate cells (CPCs) in a cohort of subjects at baseline and 1 and 12 months after surgery. |
| Measure the Effect of Genistein on Select Gene and Protein Expressions in Prostate Tissue | At baseline and at time of surgery | At baseline and time of surgery, tissue will be collected to measure the effect of genistein on select gene and protein expressions in prostate tissue. |
| Measurement of PSA in Serum and Plasma by Nanotechnology | At screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery | Blood will be collected to measure PSA in serum and plasma by nanotechnology at screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery. |
Countries
United States
Participant flow
Recruitment details
The study opened on October 21, 2010 with an accrual goal of 30 patients with firs the patient enrolled March 3, 2011. The study was designed as a randomized blinded drug/placebo study but was amended to a single arm drug study and accrual reduced to 18. Study closed permanently on May 28, 2014 due to low accrual with 12 patients treated on study.
Pre-assignment details
Patients entered the study and were treated in a double blinded fashion with a ration of 2:1 Genistein:Placebo. Unblinding occured if it was medically necessary otherwise blinding was maintained until the time of data review.
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Genistein Patients receive oral genistein or placebo once daily for 3 months beginning at least 2 weeks prior to radical prostatectomy.
Genistein: Given orally
Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer | 8 |
| Arm II - Placebo Patients receive oral genistein or placebo once daily for 3 months beginning at least 2 weeks prior to radical prostatectomy.
Placebo: Given orally
Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer | 4 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive Disease | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Arm II - Placebo | Arm I - Genistein |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United States | 12 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 2 / 8 | 1 / 4 |
| serious Total, serious adverse events | 1 / 8 | 0 / 4 |
Outcome results
Primary
Number of Circulating Prostate Cells (CPCs) in the Blood as Determined by qRT-PCR for PSA on RNA Extracted From PBMNCs
Blood will be collected to analyze the number of CPC's at screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery.
Time frame: At screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery
Population: Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.
Secondary
Measurement of PSA in Serum and Plasma by Nanotechnology
Blood will be collected to measure PSA in serum and plasma by nanotechnology at screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery.
Time frame: At screening, after 1-month of treatment, at surgery and at 1 and 12 months after surgery
Population: Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.
Secondary
Measure the Effect of Genistein on Select Gene and Protein Expressions in Prostate Tissue
At baseline and time of surgery, tissue will be collected to measure the effect of genistein on select gene and protein expressions in prostate tissue.
Time frame: At baseline and at time of surgery
Population: Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.
Secondary
Natural History of Circulating Prostate Cells (CPCs) in a Cohort of Subjects Prior to and Post Radical Prostatectomy
Blood will be drawn to analyze the natural history of circulating prostate cells (CPCs) in a cohort of subjects at baseline and 1 and 12 months after surgery.
Time frame: At baseline, 1 and 12 months after surgery
Population: Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.