A Phase II Study Of SB-715992 (NSC 727990) In Patients With Locally Advanced, Recurrent Or Metastatic Hepatocellular Carcinoma
Inclusion 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
