A Phase I, Dose Escalation Study to Assess the Safety and Pharmacokinetics of SB- 485232 Administered as Daily Subcutaneous Injections in Adult Patients With Solid Tumors
- Histologically or cytologically confirmed diagnosis of malignancy.
- Subjects with solid tumors must have locally advanced or metastatic disease at the
time of enrollment.
- Measurable or evaluable disease that is refractory or resistant to standard therapy
or for which there is no effective standard therapy.
- Predicted life expectancy of at least 12 weeks.
- Kinesin spindle protein (KPS) of greater than 70%.
- No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer,
radiotherapy, or surgical procedures (except for minor surgical procedures) within 4
weeks before beginning treatment with SB-485232 (6 weeks for nitrosoureas and
- Subjects must have recovered from toxicities (incurred as a result of previous
therapy) sufficiently to be entered into a Phase I study.
- Provide written informed consent.
- Absence of anti-SB-485232 antibodies.
- Hemoglobin greater than or equal to 9 g/dL.
- Absolute neutrophil count greater than or equal to 1.5 X 109 /L.
- Platelet count greater than or equal to 100 X 109 /L.
- Partial thromboplastin time (PTT) and prothrombin time/international normalized ratio
(PT/INR) within normal limits.
- Serum creatinine less than or equal to 1.5 mg/dL (135 µmol/L) or estimated creatinine
clearance greater than 50 mL/min (calculated by the Cockcroft-Gault Formula).
- Total serum bilirubin less than or equal to 1.5 mg/dL.
- Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3 X
- Sexually active males or females of reproductive capacity must use adequate
- For subjects with a history of coronary artery disease, stress test must be within
- Subjects with a history of congestive heart failure, myocardial infarction or prior
anthracycline chemotherapy must have a Multiple Gated Acquisition (MUGA) scan with a
left ventricular ejection fraction of greater than 40%.
- Women who are pregnant or are breast-feeding.
- Severe or uncontrolled infections requiring systemic antibiotic therapy.
- Any serious medical or psychiatric disorder that would interfere with subject safety
or informed consent.
- Known leptomeningeal disease or evidence of prior or current metastatic brain
- Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational
- Receiving concurrent systemic steroids.
- History of ventricular arrhythmias requiring drug or device therapy.
- Any severe concurrent disease or condition, including significant autoimmune
diseases, which in the judgment of the principal investigator, would make the subject
inappropriate for study participation.
- Any unresolved or unstable serious toxicity from prior administration of another
- Any investigational drug within 30 days or 5 half-lives (whichever is longer)
preceding the first dose of SB-485232.
- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the study.
- Received prior treatment with SB-485232.
- Poor venous access.