SB939 in Treating Patients With Locally Advanced or Metastatic Solid Tumors
RATIONALE: SB939 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of SB939 in treating patients with locally advanced or metastatic solid tumors.
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: HDAC inhibitor SB939 Other: immunoenzyme technique Other: immunohistochemistry staining method Other: immunologic technique Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry Other: pharmacological study||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer|
- Recommended phase II dose [ Time Frame: Each dose level ]Assess for safety, tolerability, toxicity profile and dose limiting toxicities
- Safety [ Time Frame: Each dose level ]Safety, tolerability, toxicity profile, dose limiting toxicities of SB939.
- Pharmacokinetic profile [ Time Frame: Cycle 1 day 1 and 15 ]Samples collected over multiple timepoints
- SB939 effects on histone H3 acetylation [ Time Frame: Cycle 1 days 1 and 15 ]Levels of AcH3 will be determined using wetern Blot, immunohistochemistry or Elisa method.
|Study Start Date:||June 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Drug: HDAC inhibitor SB939
- 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 pharmacokinetics.
- 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 toxicity.
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 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00504296
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Study Chair:||Lillian L. Siu, MD, FRCPC||Princess Margaret Hospital, Canada|