Sunitinib Malate and Capecitabine in Treating Patients With Unresectable or Metastatic Liver Cancer

The CapSul Trial: A Phase II Study of Sunitinib and Capecitabine for the Treatment of Unresectable or Metastatic Hepatocellular Carcinoma (HCC)

This phase II trial studies how well giving sunitinib malate together with capecitabine works in treating patients with unresectable or metastatic liver cancer. Sunitinib malate 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. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib malate together with capecitabine may kill more tumor cells

Study Overview

• Status: Terminated
• Conditions: Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Adult Primary Hepatocellular Carcinoma
• Intervention / Treatment: Drug: capecitabine; Drug: sunitinib malate

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the progression-free survival of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with sunitinib and capecitabine.

SECONDARY OBJECTIVES:

I. To determine the overall survival, response rate by Response Evaluation Criteria in Solid Tumors (RESIST) criteria, alpha fetoprotein (AFP) response, survival at one year, and safety and tolerability.

OUTLINE:

Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-21 and capecitabine PO twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence or disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of hepatocellular carcinoma (HCC) OR meets radiographic criteria for diagnosis of HCC without biopsy
• Liver mass at least 1 cm up to 2 cm in size: classic enhancement on 2 approved imaging modalities
• Liver mass > 2 cm in size: classic enhancement on 1 approved imaging modality
• At least one site of bidimensional measurable disease with the longest axis >= 20mm by conventional computed tomography (CT) scan or >= 10mm by spiral CT scan or >= 10mm by magnetic resonance imaging (MRI)
• Not eligible for curative intent surgery and not eligible for, or not willing to undergo, orthotopic liver transplantation
• Patient has received =< 1 prior systemic therapy
• Patient has completed treatment with surgery at least 4 weeks prior to study drug administration
• Patient has completed other cancer directed treatments including systemic chemotherapy, transarterial chemotherapy, transarterial chemoembolization or bland embolization, targeted therapy, radiotherapy, or treatment with other investigational anti-cancer agents at least 4 weeks prior to study drug administration AND has radiographic evidence of disease progression following these treatments
• Life expectancy of greater than 12 weeks
• Child-Pugh class A or B
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky > 60%)
• Platelet count >= 75,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 5 times upper limit of normal (ULN)
• Total bilirubin =< 3 times ULN
• Calculated or measured creatinine clearance >= 40 mL/min
• Prothrombin time =< 1.5 international normalized ratio (INR)
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document and comply with scheduled visits, treatment plan, laboratory testing, and other trial procedures

Exclusion Criteria:

• History of another cancer within the last 5 years with the exception of localized basal or squamous cell carcinoma of the skin or stage 1A cervical cancer
• Known brain metastases, spinal cord compression, or evidence of symptomatic brain or leptomeningeal carcinomatosis on screening CT or MRI scan
• National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Grade 2 variceal bleed within 6 weeks of registration or Grade 3 other bleed within 4 weeks of registration
• Any of the following within the 6 months prior to registration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
• Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 Grade 2
• Prolonged QTc interval on baseline electrocardiograph (EKG)
• Uncontrolled Hypertension (> 150/100 mm Hg despite optimal medical therapy)
• Severe hepatic impairment, defined as Childs-Pugh Class C
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
• Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), are allowed
• Pregnancy or breastfeeding; female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy; all female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment; male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy; the definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib or capecitabine

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: Treatment (sunitinib malate and capecitabine); Patients receive sunitinib malate PO QD on days 1-21 and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence or disease progression or unacceptable toxicity.	Drug: capecitabine; Given PO; Other Names: Xeloda; CAPE; Ro 09-1978/000; Drug: sunitinib malate; Given PO; Other Names: Sutent; SU11248; sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival	Analyzed using the Kaplan-Meier method. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progressive disease (PD) indicates at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	From the start of treatment to time of progression or death from any cause, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response by RECIST Criteria	Incidence rate of best clinical response (complete response [CR], partial response [PR], stable disease [SD], or progressive disease[PD]) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR indicates disappearance of all target lesions. PR indicates at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease indicates at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) indicates neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	From the start of the treatment until disease progression/recurrence, assessed every 3 months, up to 3 years
Median Overall Survival	Survival estimated by Kaplan-Meier method	From start of treatment until death from any cause, assessed up to 3 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Samuel Whiting, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: November 7, 2008
• First Submitted That Met QC Criteria: November 7, 2008
• First Posted (Estimate): November 10, 2008

Study Record Updates

• Last Update Posted (Actual): June 1, 2017
• Last Update Submitted That Met QC Criteria: April 27, 2017
• Last Verified: April 1, 2017

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Capecitabine; Sunitinib
• Other Study ID Numbers: 6553; NCI-2010-00605 (Registry Identifier: CTRP (Clinical Trial Reporting Program))