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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: ispinesib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ispinesib|SB-715992 will be given as a 1 hour intravenous infusion in a dose of 18 mg/m2 once every 3 weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 4 years | 
| Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is adjusted) |  | 4 years | 
| Molecular correlates on archival tumor specimens and peripheral blood mononuclear cells (PBMCs) |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer