Clinical trial NCT00487721: The Effect of High-dose Silybin-phytosome in Men With Prostate Cancer
Official title: A Pilot Biomarker Study of Oral Silybin-Phytosome Followed by Prostatectomy in Patients With Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Prostate cancer
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Sir Mortimer B. Davis - Jewish General Hospital
First posted: 2007-06-19
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients must sign an Institutional Review Board (IRB) approved informed consent
2. Age greater than 18 years old
3. Male patients with histologically documented adenocarcinoma of the prostate
4. Life expectancy greater than three months
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Adequate organ function including a total Bilirubin less than or equal to 1.5 mg/dl
7. Planned prostatectomy as treatment for prostate cancer.
8. No known metastatic disease

Exclusion Criteria:

1. Prior definitive treatment for prostate cancer with surgery or radiation therapy
2. Use of an investigational medication or device within one month of initiating study therapy.
3. Prior systemic chemotherapy for prostate cancer or any hormonal therapy for prostate cancer.
4. Any use of hormonal therapy (i.e. luteinizing hormone-releasing hormone analog) or anti-androgen therapy.
5. Any condition or any medication which may interfere with the conduct of the study as determined by the principal investigator.

Primary outcomes:
measure: Measurable Silibinin Tissue Levels
timeFrame: At the time of surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: L. Michael Glode, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Flaig 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.