The purpose of this study is to access the safety of combining sodium selenite with abiraterone and to see what doses of sodium selenite can be safely combined with abiraterone in treating castration resistant prostate cancer.
PRIMARY OBJECTIVE(S): · To determine the maximum tolerated dose (MTD) of sodium selenite when given in combination with abiraterone. SECONDARY OBJECTIVE(S): * To assess the safety and tolerability of the combination of sodium selenite and abiraterone in subjects with castration resistant prostate cancer (CRPC) * To assess the pharmacokinetics of sodium selenite * To assess changes in Prostate specific antigen (PSA) To evaluate the anti tumor activity of sodium selenite and abiraterone when given in combination as determined by biochemical progression free survival (PFS) and radiographic PFS.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Standard of Care (SOC) abiraterone (Zytiga) as per package insert. The recommended dose of ZYTIGA is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily.
11 mg tablets
SOC prednisone 5 mg PO twice daily
Dose limiting Toxicity (DLT)
Adverse events will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5. Dose limiting toxicities (DLTs) of the combination of sodium selenite plus abiraterone are defined as: * Any ≥ Grade 3 non-hematologic toxicity (possibly, probably, or definitely-related adverse event) * Any ≥ Grade 3 thrombocytopenia with bleeding * Any ≥ Grade 4 thrombocytopenia persisting \> 7 days * Any ≥ Grade 4 neutropenia persisting \> 7 days * Treatment withdrawal by participant decision, or for safety reasons as deemed necessary by the investigator The DLT outcome will be reported as the number of DLT events by dose cohort occurring within 2 weeks of the beginning of treatment, a number without dispersion.
Time frame: 2 weeks
Serious Adverse Events (SAEs
Participants will be monitored for 12 weeks of treatment, and for 4 weeks subsequent (up to 16 weeks in total), for serious adverse events. The SAE outcome will be reported as the number of SAEs by dose cohort occurring within 16 weeks of the beginning of treatment, a number without dispersion.
Time frame: 16 weeks
Sodium Selenite Pharmacokinetics
Blood levels of sodium selenite (pharmacokinetics) will be assessed at baseline and through 24 hours after the initial dose. The pharmacokinetics outcome will be reported by dose cohort as the mean blood level with standard deviation
Time frame: 1 day
Blood Levels of Prostate-specific Antigen (PSA)
Maintenance of prostate-specific antigen (PSA) levels in the blood consistent with disease control can be characterized as biochemical progression free survival (PFS). Blood PSA levels will be measured at baseline through treatment. The outcome will be reported as the PSA level by dose cohort at baseline and at the last assessment within 12 months. The values will be reported as the mean with standard deviation.
Time frame: upto 12months
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Radiographic Progression free Survival (PFS)
Progression free survival (PFS) means continued survival without disease relapse or recurrence. Status will be assessed by regular medical care radiographic scans, eg, computed tomography (CT); positron emission tomography (PET); X-rays; or other scans appropriate for each participant's medical condition, using the last radiographic assessment within 12 months after the start of treatment. Status will be determined per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as follows. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in lesion diameters * Progressive disease (PD) = 20% increase in lesion diameters, and/or 1+ new lesions * Stable disease (SD) = Small changes not meeting above criteria The outcome will be reported by dose cohort as the number of participants remaining alive without disease relapse, progression, or recurrence, a number without dispersion.
Time frame: upto 12months