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

Phase 2

Terminated

Conditions: Liver Cancer

Interventions: Drug: Sunitinib Malate

Registration Number: NCT00495625

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 33

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sunitinib Malate (SUO11248) Treatment	Sunitinib Malate	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Partial Response (PR) at Interim Analysis	On Treatment to Off Study - average of 7 months per participant	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 \[JNCI 92(3):205-216, 2000\].
Number of Participants With Stable Disease (SD) at Interim Analysis	On Treatment to Off Study - average of 7 months per participant	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 \[JNCI 92(3):205-216, 2000\].
Number of Participants With Progressive Disease (PD) at Interim Analysis	On Treatment to Off Study - average of 7 months per participant	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 \[JNCI 92(3):205-216, 2000\].

Secondary Outcome Measures

Name	Time	Method
Participant Time to Tumor Progression (TTP)	On Treatment to Off Study - average of 7 months per participant	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.
Number of Participants With Overall Survival (OS)	On Treatment to Off Study - average of 7 months per participant	Overall survival (OS) of sunitinib malate in the treatment in unresectable HCC
Number of Participants With Serious Adverse Events (SAEs)	On Treatment to Off Study - average of 7 months per participant	The toxicity of sunitinib malate in the treatment in unresectable HCC