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

Advanced Adult Primary Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00787787
• Other study ID #: 6553
• Secondary ID: NCI-2010-00605
• Status: Terminated
• Phase: Phase 2
• First received: November 7, 2008
• Last updated: May 7, 2013
• Start date: September 2008
• Est. completion date: June 2010

Study information

• Verified date: May 2013
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: June 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• sunitinib malate
Given PO
• capecitabine
Given PO

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median progression-free survival	Analyzed using the Kaplan-Meier method.	From the start of treatment to time of progression or death from any cause, assessed up to 18 weeks	No
Secondary	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)		From the start of the treatment until disease progression/recurrence, assessed every 3 months	No
Secondary	Median overall survival		From start of treatment until death from any cause, assessed up to 1 year	No
Secondary	Categorical changes in ECOG performance status		Baseline, day 1 of each course, and at the end of treatment	No
Secondary	Anti-tumor response as assessed by serial AFP measurement		Baseline, day 1 of each course, and at the end of treatment	No
Secondary	Incidence of treatment-emergent adverse events		Day 1 and day 30 after the last dose of study drug	Yes
Secondary	Toxicity as assessed by changes in laboratory values, vital signs, and physical examination findings and rated by NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0		At each clinic visit	Yes