A Phase I Study Evaluating the Efficacy and Safety of Sodium Selenite in Combination With Docetaxel in Castration-resistant Prostate Cancer
Overview
- Phase
- Phase 1
- Intervention
- Docetaxel
- Conditions
- Urologic Neoplasms
- Sponsor
- Sandy Srinivas
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- To determine the maximum tolerated dose (MTD)
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
Selenium, in the form of inorganic Sodium Selenite, may be useful for treating existing prostate cancer. This idea is based on data from our laboratory showing that 1) prostate cancer cells are more sensitive to Selenium (Sodium Selenite)-induced apoptosis than normal prostate epithelial cells, 2) Selenite induces significant growth inhibition of well established prostate cancer tumors in mice at doses that have no detectable toxicity, and 3) Selenite disrupts AR signaling, and that the inhibition of AR expression and activity by Selenite occurs via a redox mechanism involving GSH, superoxide, and Sp1. Altogether, these findings suggest that Selenium may be useful in a variety of potential indications in the natural history of prostate cancer, including both hormone sensitive and castrate resistant prostate cancer, as a single agent, or in combination with radiation, chemotherapy or conventional hormone therapy. Selenite is a potential novel inhibitor of AR expression and function in prostate cancer.
Investigators
Sandy Srinivas
Associate Professor
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed adenocarcinoma of the prostate
- •Castration-resistant prostate cancer requires the following 3 criteria:
- •Failure of first line bilateral orchiectomy or therapy with an LHRH agonist,
- •A rising PSA on 3 consecutive occasions at least 1 week apart (but not limited to the 30 day screening period), AND
- •A castrate level of testosterone (\<50ng/dL)
- •PSA doubling time (PSADT) \> 1 months
- •Failure on docetaxel chemotherapy as defined by a rising PSA .
- •A minimum PSA of 2 ng/mL
- •Age \>=18 years
- •Life expectancy greater than 6 months
Exclusion Criteria
- •Radiotherapy for prostate cancer within 28 days prior to Day
- •More than 1 prior chemotherapy
- •Inadequate organ function, as evidenced by any of the following at screening:
- •Absolute neutrophil count (ANC) \< 1500/uL
- •Platelet count \<= 100 x 10\^9/L
- •Total bilirubin \>= ULN
- •AST, and/or ALT \> 1.5 x the upper limit of normal (ULN) with a concomitant alkaline phosphastase \>2.5 X ULN
- •Serum creatinine \> 2.0 mg/dL
- •Hemoglobin \< 9 g/dL
- •Men with reproductive potential who do not agree to use an accepted and effective method of contraception during the study treatment period and for at least 3 months after completion of the study treatment.
Arms & Interventions
combination sodium selenite and docetaxel
Intervention: Docetaxel
combination sodium selenite and docetaxel
Intervention: Biosyn
combination sodium selenite and docetaxel
Intervention: Prednisone
Outcomes
Primary Outcomes
To determine the maximum tolerated dose (MTD)
Time Frame: 1 cycle
To determine the safety and tolerability of the combination sodium selenite and docetaxel after 4 cycles of combination therapy using the NCI Common Toxicity Criteria v3.0 grading system for adverse events
Time Frame: after 4 cycles of combination therapy