Clinical trial NCT00095992: SB-715992 in Treating Patients With Locally Advanced, Recurrent, or Metastatic Liver Cancer
Official title: A Phase II Study Of SB-715992 (NSC 727990) In Patients With Locally Advanced, Recurrent Or Metastatic Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-11-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Response
timeFrame: 4 years
Secondary outcomes:
measure: Toxicity
timeFrame: 4 years
measure: Pharmacokinetics at day 1 of course 1 (day 1 of course 2 if dose is adjusted)
timeFrame: 4 years
measure: Molecular correlates on archival tumor specimens and peripheral blood mononuclear cells (PBMCs)
timeFrame: 4 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Jennifer Knox, MD
role: STUDY_CHAIR
affiliation: British Columbia Cancer Agency
name: Sharlene Gill, MD
role: STUDY_CHAIR
References:
citation: 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.