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

Advanced Adult Primary Liver Cancer Clinical Trial

Official title:

A Phase II Trial of Dasatinib (BMS-354825) in Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00459108
• Other study ID #: NCI-2009-00224
• Secondary ID: NCI-2009-00224CD
• Status: Terminated
• Phase: Phase 2
• First received: April 9, 2007
• Last updated: March 20, 2018
• Start date: April 2007
• Est. completion date: April 2011

Study information

• Verified date: March 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adult Primary Hepatocellular Carcinoma
• Advanced Adult Primary Liver Cancer
• Carcinoma
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Recurrent Adult Primary Liver Cancer

Intervention

Drug:
• dasatinib
Given orally

Locations

Country	Name	City	State
United States	University of Southern California, Norris	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate (Complete and Partial Response)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Response = CR + PR	4 months
Primary	Four Month Progression-free Survival (PFS)	Progression-free survival calculated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	4 months
Secondary	Median Progression-free Survival	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Until disease progression or death, up to 4 years
Secondary	Overall Survival	Estimated using the product-limit method of Kaplan and Meier.	Up to 4 years
Secondary	Safety and Tolerability	Summarize observed grade 3 and higher toxicities related to dasatanib. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were used for reporting.	Up to 4 years