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

Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095992
• Other study ID #: I168
• Secondary ID: CAN-NCIC-IND168C
• Status: Completed
• Phase: Phase 2
• Start date: March 8, 2005
• Est. completion date: September 22, 2008

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 22, 2008
• Est. primary completion date: September 26, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Cancer
• Liver Neoplasms

Intervention

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

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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 Canad — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response		4 years
Secondary	Toxicity		4 years
Secondary	Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is adjusted)		4 years
Secondary	Molecular correlates on archival tumor specimens and peripheral blood mononuclear cells (PBMCs)		4 years