Dasatinib in Treating Patients With Advanced Liver Cancer That Cannot Be Removed by Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00459108
First received: April 9, 2007
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Drug: dasatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Dasatinib (BMS-354825) in Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Response rate (complete and partial response) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median PFS [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: April 2007
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given orally
Other Names:
  • BMS-354825
  • Sprycel

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459108

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Heinz-Josef Lenz City of Hope Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00459108     History of Changes
Other Study ID Numbers: NCI-2009-00224, NCI-2009-00224, CDR0000538220, PHII-83, PHII-83, 7792, N01CM62201, N01CM62209
Study First Received: April 9, 2007
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014