Clinical trial NCT00459108: Dasatinib in Treating Patients With Advanced Liver Cancer That Cannot Be Removed by Surgery
Official title: A Phase II Trial of Dasatinib (BMS-354825) in Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-04-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well dasatinib works in treating patients with advanced liver cancer that cannot be removed by surgery. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the progression-free survival (PFS) rate and response rate (complete and partial response) at 4 months in patients with unresectable advanced hepatocellular carcinoma treated with dasatinib.

SECONDARY OBJECTIVES:

I. Determine the median PFS and overall survival of patients treated with this drug.

II. Assess the toxicity and tolerability of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3-6 months thereafter.

Eligibility criteria: Criteria:

* WBC \>= 3,000/mm\^3
* LVEF normal
* Histologically or cytologically confirmed hepatocellular carcinoma; Advanced disease, unresectable disease, no Childs C criteria
* Measurable disease, defined as \>= 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques or \>= 10 mm by spiral CT scan
* Not a candidate for percutaneous ethanol injection or radiofrequency ablation (RFA)
* Prior transarterial chemoembolization, ethanol, and RFA allowed if new lesions are present in the liver and there are no other sites of disease
* No pleural effusion or ascites requiring paracentesis within the past 4 weeks
* No known brain metastases
* ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
* Life expectancy \> 3 months
* Absolute neutrophil count \>= 1,500/mm\^3
* Platelet count \>= 75,000/mm\^3
* Bilirubin =\< 2 times upper limit of normal (ULN)
* AST and ALT =\<2.5 times ULN (5 times ULN if liver involvement by tumor)
* Creatinine =\< 2 times ULN
* PT =\< 1.5 times ULN (no anticoagulation)
* Albumin \>= 2.5 mg/dL
* No history of allergic reactions attributed to compounds of similar chemical or biological composition to dasatinib
* No evidence of encephalopathy
* No condition that would preclude ability to swallow and retain dasatinib tablets, including any of the following:

  * Gastrointestinal tract disease resulting in an inability to take oral medication;
  * Requirement for IV alimentation;
  * Prior surgical procedures affecting absorption:
  * Active peptic ulcer disease
* No clinically significant ECG abnormalities
* No clinically significant cardiovascular disease, including any of the following:

  * Myocardial infarction or ventricular tachyarrhythmia within the past 6 months;
  * Prolonged QTc \>= 480 msec (Fridericia correction);
  * Major conduction abnormality (unless cardiac pacemaker is present)
* No other uncontrolled illness, including, but not limited to, any of the following:

  * Ongoing or active infection;
  * History of significant bleeding disorder, including congenital (von Willebrand's disease) or acquired disorders (antifactor VIII antibodies);
  * Psychiatric illness or social situation that would preclude study compliance
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Recovered from all prior therapy
* One prior systemic chemotherapy regimen allowed
* Prior cryosurgery allowed
* More than 4 weeks since prior transarterial chemoembolization
* More than 4 weeks since prior radiotherapy
* Prior or concurrent localized palliative radiotherapy (i.e., bony metastasis) allowed provided it was administered for =\< 3 days
* At least 7 days since prior and no concurrent antithrombotic and/or antiplatelet agents (e.g., warfarin, heparin, low molecular weight heparin, acetylsalicylic acid, and/or ibuprofen)
* At least 7 days since prior and no concurrent agents with proarrhythmic potential
* At least 7 days since prior and no concurrent medications or substances that are potent inhibitors or inducers of CYP3A4
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent embolization or chemoembolization
* No concurrent systemic antacids (H2 receptor antagonists or proton pump inhibitors)
* Locally active antacids allowed provided they are held for 2 hours before and 2 hours after dasatinib dose
* No other concurrent investigational agents
* No other concurrent anticancer agents or therapies

Primary outcomes:
measure: Response Rate (Complete and Partial Response)
timeFrame: 4 months
measure: Four Month Progression-free Survival (PFS)
timeFrame: 4 months
Secondary outcomes:
measure: Median Progression-free Survival
timeFrame: Until disease progression or death, up to 4 years
measure: Overall Survival
timeFrame: Up to 4 years
measure: Safety and Tolerability
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California, Norris
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Heinz-Josef Lenz
role: PRINCIPAL_INVESTIGATOR
References: