dose-escalation study of sb-485232 administered as daily subcutaneous injections in adults with solid tumors

Conditions: Solid Tumor Cancer

Summary: this is a phase i, open-label, dose-escalation study of sb-485232. subjects will receive sb-485232 administered as subcutaneous injections daily for 14 days. dose escalation (enrollment into the next cohort) cannot occur until all three subjects have completed the previous cohort; 5 doses will be tested. an additional dosing regimen has been added to evaluate higher doses given twice weekly for 7 weeks. therefore, the full evaluation period for each patient will extend out to approximately eleven weeks after the first day of sb-485232 dosing.


Eligibility criteria:
inclusion criteria: * 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 mitomycin c). * 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 uln. * sexually active males or females of reproductive capacity must use adequate contraception. * for subjects with a history of coronary artery disease, stress test must be within normal limits. * 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%. exclusion criteria: * 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 disease. * receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy. * 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 investigational drug. * 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.

Keywords: il-18 subcutaneous pharmacokinetics phase 1