Sunitinib and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

Phase 2

Terminated

Conditions: Liver Cancer

Interventions: Drug: doxorubicin hydrochloride
Drug: sunitinib malate
Other: laboratory biomarker analysis
Procedure: hepatic artery embolization
Procedure: quality-of-life assessment

Registration Number: NCT00524316

Lead Sponsor: Roswell Park Cancer Institute

Brief Summary: RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs, such as doxorubicin, near the tumor. Giving sunitinib together with chemoembolization may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving sunitinib together with chemoembolization works in treating patients with liver cancer that cannot be removed by surgery.

Detailed Description: OBJECTIVES:

Primary

* To determine the progression-free survival at 4 months of patients treated with this regimen.

Secondary

* To determine overall survival of these patients.

* To determine if dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to measure decrease in tumor perfusion and vascular permeability as a result of treatment with sunitinib malate in combination with TACE, and if it can be useful in prognosis.

* To examine the safety and tolerability of this regimen.

* To determine if a change in circulating endothelial precursor cell number and total monocyte count on days 3, 8, 10, and 35 of therapy (as compared with levels at baseline) and decrease in soluble vascular endothelial growth factor receptor-2 in serum on days 8 (before TACE), 10, and 35 of therapy (as compared with baseline) correlate with improved response and survival.

* To determine the effect of this therapy on quality of life as measured by the FACT-HEP scale prior to each course of therapy.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses. Patients undergo hepatic artery chemoembolization with doxorubicin hydrochloride on day 8 of course 1 only. Treatment with sunitinib malate repeats every 6 weeks\* in the absence of disease progression or unacceptable toxicity.

NOTE: \*Course 1 is 7 weeks in duration; all subsequent courses are 6 weeks in duration.

Blood samples are collected at baseline and periodically during study to measure circulating endothelial precursor cell levels, total monocyte count, and soluble vascular endothelial growth factor receptor-2.

Quality of life is assessed by the FACT-HEP scale at baseline, prior to each course of treatment, and then at the completion of treatment.

After completion of study treatment, patients are followed every 6 months.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sunitinib	laboratory biomarker analysis	oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses
Sunitinib	hepatic artery embolization	oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses
Sunitinib	sunitinib malate	oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses
Sunitinib	quality-of-life assessment	oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses
Sunitinib	doxorubicin hydrochloride	oral sunitinib malate once daily on days 1-7 and 15-35 in course 1 and on days 1-28 in all subsequent courses

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months	median progression free survival in months

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months	median survival in months
Tumor Marker Response (AFP)	Baseline, week 7 and every 6 weeks after	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; Overall Response (OR) = CR + PR.
Tissue Perfusion, Ktrans, IAUC, and Percent Viable Tumor as Measured by DCE-MRI at Baseline and on Days 8 (Before Transarterial Chemoembolization), 10, and 35	Baseline, day 8, day 10, day 28 and day 35
Safety and Tolerability	Daily while on treatment through study completion, an average of 1 year	Number of participants with adverse advent. Please refer to adverse event reporting for more detail.
Assess the Change in the Quality of Life Among Patients Using the FACTHep (Version 4) for Hepatobiliary Cancers.	Baseline and Cycle 2	We utilized the FACT-HEP TOTAL SCORE (version 4) quality-of-life scale, which is a 45 item scale ranging from 96-178. Higher scores reflect better quality of life. No subscales were analyzed.