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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00095992
First received: November 9, 2004
Last updated: September 26, 2011
Last verified: September 2011

November 9, 2004
September 26, 2011
November 2004
August 2008   (final data collection date for primary outcome measure)
Response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00095992 on ClinicalTrials.gov Archive Site
  • Toxicity [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is adjusted) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Molecular correlates on archival tumor specimens and peripheral blood mononuclear cells (PBMCs) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Jan 15; [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
September 2008
August 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00095992
I168, CAN-NCIC-IND168, CDR0000391839
No
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
NCIC Clinical Trials Group
September 2011

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