Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief summary
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.
Detailed description
OBJECTIVES: Primary * To determine the recommended phase II dose of oral SB939 in patients with solid tumors. Secondary * 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.
Interventions
SB939 will be administered initially for 3 consecutive days every other week at the first dose level and then for 5 consecutive days every other week at escalating doses.
OTHERimmunoenzyme technique
OTHERimmunohistochemistry staining method
OTHERimmunologic technique
OTHERlaboratory biomarker analysis
OTHERmass spectrometry
OTHERpharmacological study
Sponsors
S*BIO
NCIC Clinical Trials Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Histologically or cytologically confirmed locally advanced or metastatic solid tumor * Refractory to standard therapy or for which conventional therapy is not reliably effective
Exclusion criteria
* Patients with documented CNS metastases PATIENT CHARACTERISTICS: Inclusion criteria: * ECOG performance status of 0, 1, or 2 * Must have a life expectancy of ≥ 12 weeks * Granulocytes (AGC) ≥ 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Bilirubin ≤ upper limit of normal (ULN) * AST and ALT ≤ 2.5 x ULN (\< 5 x ULN if liver metastases are present) * Serum creatinine ≤ 1.2 x ULN OR creatinine clearance ≥ 60 mL/min * QTc ≤ 450 msec * LVEF ≥ 50% by ECHO or MUGA * Troponin I or T ≤ ULN * Must be within 1½ hour's driving distance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase II dose | Each dose level | Assess for safety, tolerability, toxicity profile and dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile | Cycle 1 day 1 and 15 | Samples collected over multiple timepoints |
| SB939 effects on histone H3 acetylation | Cycle 1 days 1 and 15 | Levels of AcH3 will be determined using wetern Blot, immunohistochemistry or Elisa method. |
| Safety | Each dose level | Safety, tolerability, toxicity profile, dose limiting toxicities of SB939. |
Countries
Canada
Outcome results
None listed