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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00095992
Recruitment Status : Completed
First Posted : November 9, 2004
Last Update Posted : September 27, 2011
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

November 9, 2004
November 9, 2004
September 27, 2011
November 2004
August 2008   (Final data collection date for primary outcome measure)
Response [ Time Frame: 4 years ]
Not Provided
Complete list of historical versions of study NCT00095992 on Archive Site
  • Toxicity [ Time Frame: 4 years ]
  • Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is adjusted) [ Time Frame: 4 years ]
  • Molecular correlates on archival tumor specimens and peripheral blood mononuclear cells (PBMCs) [ Time Frame: 4 years ]
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SB-715992 in Treating Patients With Locally Advanced, Recurrent, or Metastatic Liver Cancer
A Phase II Study Of SB-715992 (NSC 727990) In Patients With Locally Advanced, Recurrent Or Metastatic Hepatocellular Carcinoma

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.


  • 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.

Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Liver Cancer
Drug: ispinesib
SB-715992 will be given as a 1 hour intravenous infusion in a dose of 18 mg/m2 once every 3 weeks
Not Provided
Knox JJ, Gill S, Synold TW, Biagi JJ, Major P, Feld R, Cripps C, Wainman N, Eisenhauer E, Seymour L. A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168). Invest New Drugs. 2008 Jun;26(3):265-72. doi: 10.1007/s10637-007-9103-2. Epub 2008 Jan 15.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
September 2008
August 2008   (Final data collection date for primary outcome measure)


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks


  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 80,000/mm^3


  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST ≤ 5 times ULN
  • Must have hepatic reserve of Child-Turcotte-Pugh class A or better


  • Creatinine clearance ≥ 60 mL/min


  • 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


  • 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


Biologic therapy

  • Not specified


  • 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


  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy

    • Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy


  • At least 4 weeks since prior major surgery
  • Prior liver transplantation allowed


  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
CDR0000391839 ( Other Identifier: PDQ )
Not Provided
Not Provided
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )
NCIC Clinical Trials Group
National Cancer Institute (NCI)
Study Chair: Jennifer Knox, MD Princess Margaret Hospital, Canada
Study Chair: Sharlene Gill, MD British Columbia Cancer Agency
Canadian Cancer Trials Group
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP