Genistein in Treating Patients With Prostate Cancer

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01126879
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 34.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage II Prostate Cancer; Stage III Prostate Cancer	Dietary Supplement: genistein; Other: placebo; Procedure: therapeutic conventional surgery	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. Determine the natural history of circulating prostate cells (CPCs) in a cohort of subjects prior to and post radical prostatectomy.

2. 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.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 2 Trial of Genistein in Men With Circulating Prostate Cancer Cells
• Actual Study Start Date: Feb 3, 2011
• Actual Primary Completion Date: May 9, 2013
• Actual Study Completion Date: Dec 28, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy.	Dietary Supplement: genistein; Given orally; Other Names: CI 75610 Genestein genisteol genisterin prunetol sophoricol ; Procedure: therapeutic conventional surgery; Radical prostatectomy for treatment of prostate cancer
Placebo Comparator: Arm II Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy.	Other: placebo; Given orally; Other Names: PLCB ; Procedure: therapeutic conventional surgery; Radical prostatectomy for treatment of prostate cancer

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: William Catalona, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT01126879
• Other Study ID Numbers: NCI 09U2; NCI-2010-00941; STU00019487; P50CA090386
• First Posted: May 20, 2010
• Last Update Posted: Sep 10, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Genistein

Study Results

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 Detail	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.

Arm/Group Title	Arm I - Genistein	Arm II - Placebo
Arm/Group Description	Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Genistein: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer	Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Placebo: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer
Period Title: Overall Study
STARTED	8	4
Started 3 Months of Genistein/Placebo	8	4
Prostatectomy or Radiation	8	4
Completed 3 Months Genistein/Placebo	4	2
COMPLETED	3	2
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Arm I - Genistein	Arm II - Placebo	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	8	4	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 62.5%	2 50%	7 58.3%
>=65 years	3 37.5%	2 50%	5 41.7%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	4 100%	12 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 25%	1 8.3%
Not Hispanic or Latino	8 100%	3 75%	11 91.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	4 100%	12 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	8 100%	4 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Number of Circulating Prostate Cells (CPCs) in the Blood as Determined by qRT-PCR for PSA on RNA Extracted From PBMNCs
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.

Arm/Group Title	Arm I - Genistein	Arm II - Placebo
Arm/Group Description	Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Genistein: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer	Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Placebo: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer
Measure Participants	0	0

2. Secondary Outcome

Title	Natural History of Circulating Prostate Cells (CPCs) in a Cohort of Subjects Prior to and Post Radical Prostatectomy
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.

Arm/Group Title	Arm I - Genistein	Arm II - Placebo
Arm/Group Description	Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Genistein: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer	Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Placebo: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer
Measure Participants	0	0

3. Secondary Outcome

Title	Measure the Effect of Genistein on Select Gene and Protein Expressions in Prostate Tissue
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.

Arm/Group Title	Arm I - Genistein	Arm II - Placebo
Arm/Group Description	Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Genistein: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer	Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Placebo: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer
Measure Participants	0	0

4. Secondary Outcome

Title	Measurement of PSA in Serum and Plasma by Nanotechnology
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for analysis of this endpoint due to the study closing before the accrual goal was met.

Arm/Group Title	Arm I - Genistein	Arm II - Placebo
Arm/Group Description	Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Genistein: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer	Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Placebo: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer
Measure Participants	0	0

Adverse Events

Time Frame	Adverse Events assessed at the following timepoints for the study: at the start of treatment, at surgery or radiation, at clinic visits occurring 1-3 months post-surgery, or post-initiation of radiation therapy, or at 3 months for those not undergoing surgery or radiation, as well as at a 4 month telephone contact.
Adverse Event Reporting Description	Adverse events were collected by patient reports
Arm/Group Title	Arm I - Genistein		Arm II - Placebo
Arm/Group Description	Patients receive oral genistein once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Genistein: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer		Patients receive an oral placebo once daily for 3 months beginning at least 1 month prior to radical prostatectomy. Placebo: Given orally Therapeutic conventional surgery: Radical prostatectomy for treatment of prostate cancer
All Cause Mortality
	Arm I - Genistein		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/4 (0%)
Serious Adverse Events
	Arm I - Genistein		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/4 (0%)
Cardiac disorders
Atrial Fibrillation	1/8 (12.5%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Arm I - Genistein		Arm II - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		1/4 (25%)
Cardiac disorders
Atrial Fibrillation	1/8 (12.5%)		0/4 (0%)
Investigations
INR Increased	1/8 (12.5%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	0/8 (0%)		1/4 (25%)
Nervous system disorders
Dizziness	0/8 (0%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Large pimple	0/8 (0%)		1/4 (25%)
Surgical and medical procedures
Emergency right inguinal repair	1/8 (12.5%)		0/4 (0%)

Limitations/Caveats

The study was closed by an internal safety and data monitoring committee due to slow accrual of the study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.