Prostate CancerPhase 2NCT00487721
The Effect of High-dose Silybin-phytosome in Men With Prostate Cancer
A Phase 2 study testing Silibin-Phytosome in people with Prostate Cancer, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Silibin-Phytosome
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Nov 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80010
About this study
Official title: A Pilot Biomarker Study of Oral Silybin-Phytosome Followed by Prostatectomy in Patients With Localized Prostate Cancer
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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- Silibin-Phytosome
- Keywords
- Prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silibin-PhytosomeDrug
Also called Silymarin, silibinin, milk thistle
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.
| Study group | Role | What they receive |
|---|---|---|
| Silibin-Phytosome | Experimental | Subjects in this group will take Silibin-Phytosome 13 grams daily, in three divided doses for 2-10 weeks. Receives: Drug: Silibin-Phytosome |
| Control | No intervention | Patients in this arm will not take any intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurable Silibinin Tissue Levels
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.
Measured: At the time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2007 (estimated)
- Study startAug 2006
- Primary completionSep 2007
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Sir Mortimer B. Davis - Jewish General Hospital
- Responsible party
- Sponsor
- Investigators
- L. Michael Glode, M.D., Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00487721
- Sponsor's protocol ID
- 05-1076.cc
- Status last verified
- Mar 2014
- First submitted
- 16 Jun 2007
- Last updated
- 31 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS, Pierson AS, Agarwal R, Glode LM. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs. 2007 Apr;25(2):139-46. doi: 10.1007/s10637-006-9019-2. Epub 2006 Nov 1.
PubMed 17077998Flaig TW, Glode M, Gustafson D, van Bokhoven A, Tao Y, Wilson S, Su LJ, Li Y, Harrison G, Agarwal R, Crawford ED, Lucia MS, Pollak M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate. 2010 Jun 1;70(8):848-55. doi: 10.1002/pros.21118.
PubMed 20127732
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Biomarker Study of Oral Silybin-Phytosome Followed by Prostatectomy in Patients With Localized Prostate Cancer
- ClinicalTrials.gov ID
- NCT00487721
- Acronym / sponsor ID
- 05-1076.cc
- Conditions
- Prostate Cancer
- Keywords
- Prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Sir Mortimer B. Davis - Jewish General Hospital
- Study start
- Aug 2006
- Primary completion
- Sep 2007 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 19 Jun 2007 (estimated)
- Results
- Posted 28 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Silibin-Phytosome | Experimental | Drug: Silibin-PhytosomeSubjects in this group will take Silibin-Phytosome 13 grams daily, in three divided doses for 2-10 weeks. |
| Control | No intervention | –Patients in this arm will not take any intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Silibin-PhytosomeAlso: Silymarin, silibinin, milk thistleSubjects 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. | Drug | Silibin-Phytosome |
Primary outcome
Measurable Silibinin Tissue Levels
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17077998Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS, Pierson AS, Agarwal R, Glode LM. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs. 2007 Apr;25(2):139-46. doi: 10.1007/s10637-006-9019-2. Epub 2006 Nov 1.
- Derived from this study: PubMed 20127732Flaig TW, Glode M, Gustafson D, van Bokhoven A, Tao Y, Wilson S, Su LJ, Li Y, Harrison G, Agarwal R, Crawford ED, Lucia MS, Pollak M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate. 2010 Jun 1;70(8):848-55. doi: 10.1002/pros.21118.
- Genitourinary care team at the University of ColoradoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
L. Michael Glode, M.D. principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Silibin-Phytosome in people with Prostate Cancer, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurable Silibinin Tissue Levels (time frame: At the time of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00487721, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2014.