A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer
- To determine the recommended phase II dose of oral SB939 in patients with solid tumors.
- To determine the toxic effects of SB939 and its association with dose and
- To assess the pharmacokinetic profile of SB939.
- To assess preliminary evidence of antitumor effects of SB939 in patients with
measurable disease as documented by objective response.
- To establish proof-of-principle for SB939 effects on histone acetylation by evaluation
of histone acetylation and other biomarkers in peripheral blood mononuclear cells
(PBMCs) at all dose levels.
OUTLINE: Patients receive oral SB939 once daily on days 1-5 and 15-19. Treatment repeats
every 28 days for up to 6 courses in the absence of disease progression or unacceptable
Patients undergo blood sample collection periodically during course 1 for pharmacokinetic
and pharmacodynamic studies. Samples are analyzed for levels of SB939 via LC-MS/MS method
and levels of acetylated histone 3 (AcH3), target effect, downstream consequences, and tumor
response via western blot, immunohistochemistry, or ELISA methods.
After completion of study treatment, patients are followed at 4 weeks and then every 3
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose
Assess for safety, tolerability, toxicity profile and dose limiting toxicities
Each dose level
Lillian L. Siu, MD, FRCPC
Princess Margaret Hospital, Canada
Canada: Health Canada