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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Adult Primary Hepatocellular Carcinoma
• Intervention / Treatment: Drug: dasatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California, Norris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Dasatinib; Patients receive oral dasatinib at 70 mg 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Overall Survival	Estimated using the product-limit method of Kaplan and Meier.	Up to 4 years
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Heinz-Josef Lenz, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: April 9, 2007
• First Submitted That Met QC Criteria: April 9, 2007
• First Posted (Estimate): April 11, 2007

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: March 20, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: NCI-2009-00224 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); CDR0000538220; PHII-83 (Other Identifier: City of Hope Medical Center); 7792 (Other)