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.

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