sb-715992 in treating patients with locally advanced, recurrent, or metastatic liver cancer

Conditions: Liver Cancer

Summary: rationale: drugs used in chemotherapy, such as sb-715992, work in different ways to stop tumor cells from dividing so they stop growing or die. purpose: this phase ii trial is studying how well sb-715992 works in treating patients with locally advanced, recurrent, or metastatic liver cancer.

objectives: * determine the efficacy of sb-715992, in terms of response rate and stable disease rate, in patients with locally advanced, recurrent, or metastatic hepatocellular carcinoma. * determine the toxicity of this drug in these patients. * determine the early progression rate and response duration in patients treated with this drug. * determine the pharmacokinetics of this drug in these patients. * correlate pharmacokinetics with safety and efficacy of this drug in these patients. * correlate tumor expression of β-tubulin and kinesin spindle protein with clinical outcomes in patients treated with this drug. outline: this is a non-randomized, multicenter study. patients receive sb-715992 iv over 1 hour on day 1. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. all patients are followed at 4 weeks. patients with ongoing stable or responding disease are followed every 3 months until relapse. projected accrual: a total of 15-30 patients will be accrued for this study within 12-14 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed hepatocellular carcinoma * locally advanced, recurrent, or metastatic disease * histologically confirmed disease must have archival paraffin-fixed tumor specimen available * measurable disease * at least 1 unidimensionally measurable site of disease ≥ 20 mm by x-ray, physical exam, or non-spiral ct scan or ≥ 10 mm by spiral ct scan * outside of previously irradiated area * patients whose sole site of disease is in a previously irradiated field are eligible provided there is evidence of disease progression or new lesions documented in the irradiated field * bone metastases are not considered measurable disease * not curable by standard therapies * no cholangiocarcinoma patient characteristics: age * 18 and over performance status * ecog 0-2 life expectancy * at least 12 weeks hematopoietic * absolute granulocyte count ≥ 1,500/mm\^3 * platelet count ≥ 80,000/mm\^3 hepatic * bilirubin ≤ 2 times upper limit of normal (uln) * ast ≤ 5 times uln * must have hepatic reserve of child-turcotte-pugh class a or better renal * creatinine clearance ≥ 60 ml/min cardiovascular * no myocardial infarction within the past 6 months * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia * no active cardiomyopathy * no uncontrolled hypertension other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no clinical evidence of encephalopathy * no ongoing or active infection * no history of allergic reaction attributed to compounds of similar chemical or biological composition to sb-715992 * no psychiatric illness or social situation that would preclude study compliance * no other uncontrolled illness * no other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years prior concurrent therapy: biologic therapy * not specified chemotherapy * at least 4 weeks since prior intra-hepatic chemotherapy as a component of trans-arterial chemoembolization and recovered * documented disease progression * no prior systemic chemotherapy endocrine therapy * not specified radiotherapy * see disease characteristics * at least 4 weeks since prior radiotherapy * exceptions may be made for low-dose, nonmyelosuppressive radiotherapy surgery * at least 4 weeks since prior major surgery * prior liver transplantation allowed other * no other prior systemic therapy * at least 4 weeks since prior local ablative therapy (e.g., radiofrequency ablation or ethanol injection) and recovered * documented disease progression * more than 28 days since prior investigational agents * more than 14 days since prior and no concurrent use of any of the following cyp3a4 inhibitors or inducers: * clarithromycin * erythromycin * troleandomycin * itraconazole * ketoconazole * fluconazole (dose \> 200 mg/day) * voriconazole * nefazodone * fluvoxamine * verapamil * diltiazem * grapefruit juice * bitter orange * phenytoin * carbamazepine * phenobarbital * oxcarbazepine * rifampin * rifabutin * rifapentine * hypericum perforatum (st. john's wort) * modafinil * at least 6 months since prior and no concurrent amiodarone * no concurrent combination antiretroviral therapy for hiv-positive patients * no other concurrent anticancer therapy * no other concurrent investigational agents

Keywords: adult primary hepatocellular carcinoma advanced adult primary liver cancer localized unresectable adult primary liver cancer recurrent adult primary liver cancer