Biomarker Analysis in Sorafenib Treated Hepatocellular Carcinoma Patients

Study Overview
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Brief Summary
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To explore biomarkers predictive of clinical response to sorafenib in unresectable hepatocellular carcinoma using the Prometheus Platform To analyze expression and activation status of receptor tyrosine kinases in signal transduction pathways in FNA samples and circulating tumor cells. To identify negative predictive markers to sorafenib. To elucidate signal transduction pathway attributable to sorafenib resistance. To monitor changes in the RTK activation status during sorafenib treatment using circulating tumor cells. To analyze correlation between the quantity of circulating tumor cells and circulating endothelial cell precursors and treatment response to sorafenib.

Official Title
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Biomarker Analysis in Sorafenib Treated Hepatocellular Carcinoma Patients

Conditions
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Hepatocellular Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed hepatocellular carcinoma (HCC) or a combination of radiologically compatible finding to HCC, alpha-fetoprotein > 400ng/mL and liver cirrhosis Inoperable disease as defined by (Localized disease in a portion of the liver that doses not allow the possibility of complete surgical removal of the tumor with a clear resection margin OR Presence of extra-hepatic disease OR Main portal vein or hepatic vein involvement (invasion or tumor thrombus) OR The HCC must not be amenable to intra-arterial therapy or local ablative therapy) Minimum life expectancy of 12 weeks Age > 18 years. ECOG Performance Status of ≤ 2 Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: (Hemoglobin > 9.0 g/dl,Absolute neutrophil count>1,500/mm3, Platelet count>75,000/μl,Total bilirubin < 1.5 times the upper limit of normal,ALT and AST < 5 x upper limit of normal,Albumin ≥ 3g/dL,PT-INR/PTT < 1.5 x upper limit of normal,Serum creatinine < 1.5 x upper limit of normal or Creatinine clearance ≥ 50mL/min) Signed and dated informed consent before the start of specific protocol procedures. FNA will be performed in patients with feasible biopsy site Exclusion Criteria: Decompensated cirrhosis or stage C (Index > 10) according to the Child-Pugh Classification Other concomitant anticancer agent, including Tamoxifen and Interferon Active clinically serious infections (> grade 2 CTCAE version 3.0) History of organ allograft Patients with evidence or history of bleeding diasthesis Patients undergoing renal dialysis Radiotherapy during study or within 4 weeks of start of study drug. Prior exposure to the study drug. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hepatocellular carcinoma patients treated with sorafenib<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers predictive | To explore biomarkers predictive of clinical response to sorafenib in unresectable hepatocellular carcinoma using the Prometheus Platform A. To analyze expression and activation status of receptor tyrosine kinases in signal transduction pathways in FNA samples and circulating tumor cells B. To identify negative predictive markers to sorafenib | 36months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signal transduction pathway | To elucidate signal transduction pathway attributable to sorafenib resistance. | 36months | 
| The RTK activation status. | To monitor changes in the RTK activation status during sorafenib treatment using circulating tumor cells. | 36months |