SB-715992 in Treating Patients With Locally Advanced, Recurrent, or Metastatic Liver Cancer

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