The Effect of High-dose Silybin-phytosome in Men With Prostate Cancer
Study Details
Study Description
Brief Summary
Silibinin has demonstrated anti-cancer activity in the laboratory for several different cancer types, including prostate cancer. Silibinin was originally obtained from milk thistle. Silybin-Phytosome, an oral form of silibinin, has been tested previously in prostate cancer patients to determine the safety of high-dose treatment. This study is for men with prostate cancer who are planning to have their prostate surgically removed. Participants will be given Silybin-Phytosome three times a day from enrollment in the study until the time of their surgery. Participation in this study will not affect the timing of surgery. We obtain blood and urine samples at the start and completion of the trial in addition to prostate tissue from the surgery. These samples will be analyzed for the effect of Silybin-Phytosome at the end of the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Prostate cancer is the most common invasive malignancy and the second leading cause of cancer death in American males. In 2005, an estimated 230,000 men will be diagnosed and 30,000 will die from prostate cancer. The current estimated risk of developing prostate cancer is 1 in 6 men. Carcinogenesis and neoplastic progression of prostate cancer depend on both genetic and epigenetic factors; a multi-step process leads to progression from an androgen-dependent, non-metastatic phenotype to a more malignant, metastatic, androgen-independent phenotype.
Treatment options for localized prostate cancer include watchful waiting, surgical prostatectomy, or targeted irradiation. The latter two treatments can cure cancers that are confined to the prostate gland, yet many patients have occult metastasis at the time of presentation, particularly to the bone or regional lymph nodes.
Advanced prostate cancer with metastases presents a difficult therapeutic problem. Those who have disease progression with hormonal therapy have limited options. Patients initially treated with the combination of a Luteinizing Hormone Releasing Hormone (LHRH) analog and a synthetic antiandrogen occasionally respond to withdrawal of the anti-androgen. Chemotherapy is also an option in this setting, with docetaxel-based therapy having a small survival advantage in patients with hormone refractory prostate cancer.
There is clearly a need for more effective regimens for patients with prostate cancer. With the current limitation in treatment options, there has been a renewed public and scientific interest in the use of less toxic herbal preparations in the treatment of cancer. Herbal supplements may play an especially important role in prostate cancer, considering its high incidence and oftentimes slow progression. However, before physicians can confidently recommend dietary supplementation, further scientific investigation is required.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Silibin-Phytosome Subjects in this group will take Silibin-Phytosome 13 grams daily, in three divided doses for 2-10 weeks. |
Drug: Silibin-Phytosome
Subjects will take Silibin-Phytosome for 2-10 weeks. The dose of Silibin-Phytosome is 13 grams daily, in three divided doses. Patients will be asked to mix 1 level teaspoon and 1 heaping ¼ teaspoon of Silybin-Phytosome powder into 6 tablespoons of applesauce for each dose.
Other Names:
|
| No Intervention: Control Patients in this arm will not take any intervention. |
Outcome Measures
Primary Outcome Measures
- Measurable Silibinin Tissue Levels [At the time of surgery]
To determine if measurable silibinin tissue levels are detectable in the prostate glands of men treated with Silybin-Phytosome administered according to the protocol. Analysis of silibinin in human fluid and tissue samples was carried out by Liquid chromatography - mass spectrometric (LC/MS/MS) following liquid extraction. Briefly, sample was extracted in acidified ethyl acetate by vortex. Following centrifugation, the organic layer was evaporated to dryness in a rotary evaporator and the samples were dissolved in acetonitrile/ammonium acetate with acetic acid for analysis. Sample analysis was done using an Applied Biosystems 3200 Q-Trap 1 triple quadrupole mass spectrometer with an Agilent 1100 Liquid Chromatography system and HTC-PAL Leap Autosampler. Quantitation of silibinin in samples was done by internal standard reference and batch analysis verified by the inclusion of spiked quality control samples in the appropriate matrix.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must sign an Institutional Review Board (IRB) approved informed consent
-
Age greater than 18 years old
-
Male patients with histologically documented adenocarcinoma of the prostate
-
Life expectancy greater than three months
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
-
Adequate organ function including a total Bilirubin less than or equal to 1.5 mg/dl
-
Planned prostatectomy as treatment for prostate cancer.
-
No known metastatic disease
Exclusion Criteria:
-
Prior definitive treatment for prostate cancer with surgery or radiation therapy
-
Use of an investigational medication or device within one month of initiating study therapy.
-
Prior systemic chemotherapy for prostate cancer or any hormonal therapy for prostate cancer.
-
Any use of hormonal therapy (i.e. luteinizing hormone-releasing hormone analog) or anti-androgen therapy.
-
Any condition or any medication which may interfere with the conduct of the study as determined by the principal investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Colorado Hospital | Aurora | Colorado | United States | 80010 |
Sponsors and Collaborators
- University of Colorado, Denver
- Sir Mortimer B. Davis - Jewish General Hospital
Investigators
- Principal Investigator: L. Michael Glode, M.D., University of Colorado, Denver
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 05-1076.cc
Study Results
Participant Flow
| Recruitment Details | Twelve patients were recruited from the urologic oncology clinic at the University of Colorado Hospital between October of 2006 and October of 2007. |
|---|---|
| Pre-assignment Detail | All patients were newly diagnosed with prostate cancer and planning to pursue surgical radical prostatectomy. Patients were excluded from participation if they had received previous treatment for prostate cancer or if their surgery was scheduled within 14 days. |
| Arm/Group Title | Silibin-Phytosome | Control |
|---|---|---|
| Arm/Group Description | Subjects in this group received silybin-phytosome for 2-10 weeks, depending on the time from enrollment until the time of the prostatectomy. The dose of silybin-phytosome was 13 g daily in three divided doses. | Subjects in the control arm did not receive any treatment or placebo. |
| Period Title: Overall Study | ||
| STARTED | 6 | 6 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Silibin-Phytosome | Control | Total |
|---|---|---|---|
| Arm/Group Description | Subjects in this group received silybin-phytosome for 2-10 weeks, depending on the time from enrollment until the time of the prostatectomy. The dose of silybin-phytosome was 13 g daily in three divided doses. | Subjects in the control arm did not receive any treatment or placebo. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 12 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
5
83.3%
|
4
66.7%
|
9
75%
|
| >=65 years |
1
16.7%
|
2
33.3%
|
3
25%
|
| Age (Years) [Mean (Full Range) ] | |||
| Mean (Full Range) [Years] |
56.5
|
57.5
|
57
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
6
100%
|
6
100%
|
12
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
6
100%
|
6
100%
|
12
100%
|
| 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 |
6
100%
|
6
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 (Number) [Number] | |||
| United States |
6
100%
|
6
100%
|
12
100%
|
Outcome Measures
| Title | Measurable Silibinin Tissue Levels |
|---|---|
| Description | To determine if measurable silibinin tissue levels are detectable in the prostate glands of men treated with Silybin-Phytosome administered according to the protocol. Analysis of silibinin in human fluid and tissue samples was carried out by Liquid chromatography - mass spectrometric (LC/MS/MS) following liquid extraction. Briefly, sample was extracted in acidified ethyl acetate by vortex. Following centrifugation, the organic layer was evaporated to dryness in a rotary evaporator and the samples were dissolved in acetonitrile/ammonium acetate with acetic acid for analysis. Sample analysis was done using an Applied Biosystems 3200 Q-Trap 1 triple quadrupole mass spectrometer with an Agilent 1100 Liquid Chromatography system and HTC-PAL Leap Autosampler. Quantitation of silibinin in samples was done by internal standard reference and batch analysis verified by the inclusion of spiked quality control samples in the appropriate matrix. |
| Time Frame | At the time of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol analysis was used and 6 participants that were enrolled in the study were included in the analysis. |
| Arm/Group Title | Silibin-Phytosome |
|---|---|
| Arm/Group Description | Subjects in this group received silybin-phytosome for 2-10 weeks, depending on the time from enrollment until the time of the prostatectomy. The dose of silybin-phytosome was 13 g daily in three divided doses. |
| Measure Participants | 6 |
| Number [Participants] |
3
50%
|
Adverse Events
| Time Frame | Adverse events were assessed within 7 days of the end of of the study. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Silibin-Phytosome | Control | ||
| Arm/Group Description | Subjects in this group received silybin-phytosome for 2-10 weeks, depending on the time from enrollment until the time of the prostatectomy. The dose of silybin-phytosome was 13 g daily in three divided doses. | Subjects in the control arm did not receive any treatment or placebo. | ||
All Cause Mortality |
||||
| Silibin-Phytosome | Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Silibin-Phytosome | Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 0/6 (0%) | ||
| General disorders | ||||
| Hospitalization or Prolonged Hospitalization | 1/6 (16.7%) | 0/6 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Silibin-Phytosome | Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 0/6 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 3/6 (50%) | 0/6 (0%) | ||
| Investigations | ||||
| Hyperbilirubinemia | 1/6 (16.7%) | 0/6 (0%) | ||
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dr. Thomas Flaig |
|---|---|
| Organization | University of Colorado, Denver |
| Phone | (720) 848 0655 |
| Thomas.Flaig@ucdenver.edu |
- 05-1076.cc