Sunitinib Malate (SUO11248) In Subjects W/ Metastatic And/Or Surgically Unresectable Hepatocellular Cancers (HCC)

Study Overview
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Brief Summary
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An open label multi-site phase II clinical trial of dose escalated sunitinib malate given orally once daily on days 1-28 of each 42-day cycle. Treatment will be continued until there is either disease progression or cumulative or acute toxicity which in the opinion of the treating physician compromises the ability of the patient to receive treatment or patient desire to stop treatment.

Detailed Description
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An open label multi-site phase II clinical trial of sunitinib malate given orally once daily on days 1-28 of each 42-day cycle. Sunitinib malate will be dispensed as capsules at the beginning of each treatment cycle. The dose may be escalated at the investigator's discretion. Treatment will be continued until there is either disease progression or cumulative or acute toxicity which in the opinion of the treating physician compromises the ability of the patient to receive treatment or patient desire to stop treatment. A follow up visit will be required before the beginning of every cycle every 6 weeks to assess toxicity and for physical examination. Complete blood count (CBC) and differential, comprehensive metabolic panel (including liver function tests) and alpha-feto protein (when indicated) will be obtained at every scheduled follow up visit.

Official Title
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Phase II Open-Label Study of Sunitinib Malate (SUO11248) in Adult Subjects With Metastatic and/or Surgically Unresectable Hepatocellular Cancers (HCC)

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: Sunitinib Malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 grade less than or equal to 1. Adequate organ function as defined by the following criteria: Serum aspartate transaminase (AST); serum glutamic oxaloacetic transaminase (SGOT) and serum alanine transaminase (ALT); serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin less than or equal to 1.5 x ULN Absolute neutrophil count (ANC) more than or equal to 1500/mcL Platelets more than or equal to 100,000/mcL Hemoglobin more than or equal to 9.0 g/dL Serum calcium less than or equal to 12.0 mg/dL Serum creatinine less than or equal to 1.5 x ULN Biopsy-proven disease Measurable disease radiographically Disease that is deemed surgically unresectable (awaiting orthotopic hepatic transplantation allowable) and/or metastatic Age greater or equal to 18 years Life expectancy greater than 16 weeks Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky score > 60%) Exclusion Criteria: Major surgery or radiation therapy or chemotherapy within 4 weeks of starting the study treatment NCI CTCAE version 3 grade 3 hemorrhage within 4 weeks of starting the study treatment History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening computed tomography (CT) or magnetic resonance imaging (MRI) scan Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. Known brain metastases Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2 Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450msec for males or > 470 msec for females Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy) Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. Quality of Life (QOL), are allowed Concomitant use of ketoconazole or other agents known to induce CYP3A4 Concomitant use of theophylline and phenobarbital and/or other agents metabolized by the cytochrome P450 system Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po daily for thrombo prophylaxis is 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib Malate (SUO11248) Treatment<br> | Drug: Sunitinib Malate<br>* Once daily oral doses on days 1-28 of each 42-day cycle. The dose for the first 2 cycles will be 37.5 mg daily for 28 days, every 42 days. Dose may be escalated to 50 mg daily for 28 days at the treating investigator's discretion.<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Partial Response (PR) at Interim Analysis | Partial Response at Interim Analysis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (unidimensional measurement) of target lesions, taking as reference the baseline sum longest diameter (LD). Response was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. | On Treatment to Off Study - average of 7 months per participant | 
| Number of Participants With Stable Disease (SD) at Interim Analysis | Stable Disease (SD) Rate at Interim Analysis. Stable Disease (SD): Neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. | On Treatment to Off Study - average of 7 months per participant | 
| Number of Participants With Progressive Disease (PD) at Interim Analysis | Progressive Disease Rate. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (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. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. | On Treatment to Off Study - average of 7 months per participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Time to Tumor Progression (TTP) | Investigators planned to determine the time to tumor progression (TTP) of sunitinib malate in the treatment in unresectable Hepatocellular Cancers (HCC). TTP is defined as the duration of time from start of treatment to time of progression. | On Treatment to Off Study - average of 7 months per participant | 
| Number of Participants With Overall Survival (OS) | Overall survival (OS) of sunitinib malate in the treatment in unresectable HCC | On Treatment to Off Study - average of 7 months per participant | 
| Number of Participants With Serious Adverse Events (SAEs) | The toxicity of sunitinib malate in the treatment in unresectable HCC | On Treatment to Off Study - average of 7 months per participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular cancer (HCC), Sunitinib malate, Vascular endothelial growth factor (VEGF), Platelet-derived growth factor (PDGF), Tyrosine kinases, Liver