A Phase II Study of Weekly Genexol-PM in Patients With Hepatocelluar Carcinoma After Failure of Sorafenib

Study Overview
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Brief Summary
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This study evaluate activity and safety profile of weekly Genexol-PM in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed. Patients will receive Genexol-PM on days 1, 8, and 15 every 4 weeks.

Detailed Description
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Hepatocelluar carcinoma (HCC) is a highly vascular neoplasm characterized by arterial enhancement on CT or MRI. Angiogenesis provides a target for novel prognostic and therapeutic approaches to HCC. Sorafenib is the standard 1st-line therapy shown to significantly improve overall survival in advanced HCC. However, sorafenib benefits are mostly transient and modest. In addition, sorafenib is associated with major toxicities, and about 30% of patients stop it because of intolerance. Effective therapies are needed for patients who experience progression during or after receiving sorafenib or who have sorafenib intolerance. Paclitaxel has an antiagiogenic activity and weekly administration of paclitaxel is considered to have enhanced efficacy over 3-weekly administration due to greater drug exposure or a direct antiangiogenic effect. A previous phase I study showed that weekly paclitaxel has activity in hepatocellular carcinoma and further investigation in phase II trials is warranted. Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, is believed to be superior to conventional paclitaxel in terms of the obviation of premedication and the delivery of higher paclitaxel doses without additional toxicity.

Official Title
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A Phase II Study of Weekly Genexol-PM in Patients With Advanced Hepatocelluar Carcinoma After Failure of Sorafenib

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Genexol-PM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of hepatocellular carcinoma (HCC) based on either histopathologic or cytologic findings a diagnosis of cirrhosis and HCC with classical imaging characteristics (at least a 3-phase liver protocol CT or MRI and a lesion that demonstrates arterial enhancement and washes out in the venous phase) Previous sorafenib treatment for at least 14 days and discontinuation of sorafenib treatment prior to inclusion Radiologic confirmation of disease progression during or after discontinuation of sorafenib treatment or discontinuation of sorafenib due to intolerance despite appropriate supportive care Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B disease not amenable to locoregional therapy or refractory to locoregional therapy ≥ 1 measurable lesion according to RECIST Version 1.1 ≥ 20 year of age ECOG performance status ≤ 2 Child-Pugh score ≤ 7 Informed consent prior to study Adequate organ function Hepatic: bilirubin ≤ 1.5 times upper limit of institutional normal value (ULN), AST or ALT ≤ 5 x ULN Renal: estimated creatinine clearance ≥ 60 mL/min Hematologic: hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500/μL, platelets ≥ 75,000/μL (In case of thrombocytopenia associated with hypersplenism in chronic liver disease, platelets ≥ 50,000/μL is allowed for participation at the physician's discretion.) Coagulation: prothrombin time (INR) ≤ 1.5, partial thrombin time (PTT) ≤ 5 seconds above the ULN Exclusion Criteria: Previous systemic chemotherapy for advanced disease (except previous biologic agents including VEGF inhibitors, TGF-beta inhibitors, or PD-1/PD-L1 blockers) A history o f or current hepatic encephalopathy or clinically meaningful ascites Grade 2 or more peripheral neuropathy Prior liver transplant History of any other cancer within 2 years (Patients with carcinoma in situ of any origin and patients with prior malignancy who are in remission and whose likelihood of recurrence is very low, may be eligible.) A history of treatment with taxanes (paclitaxel or docetaxel) Females who are pregnant or lactating A know allergy or hypersensitivity reaction to any of the treatment components Serious preexisting medical conditions that cannot adequately controlled with appropriate therapy

Ages Eligible for Study
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Minimum Age: 20 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: Genexol-PM<br>Genexol-PM 100 mg/m2 intravenously for 1 hour on days 1, 8, and 15 of a 28-day cycle up to 8 cycles. Patients will receive study treatment until disease progression, unacceptable toxicity, or withdrawal of consent. | Drug: Genexol-PM<br> <br> * Other names: Cremophor-free, polymeric micelle-formulated paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate at 6 months |  | Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months) | 
| Overall survival |  | Baseline to Death from Any Cause (Approximately 12 Months) | 
| Objective response rate |  | Baseline to Objective Progression (Approximately 12 Months) | 
| Adverse events | NCI-CTCAE V4.03 | Cycle 1 through Follow Up (Approximately 12 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Neoplasms, Antineoplastic Agents, Carcinoma, Hepatocellular, Genexol-PM, Neoplasms by Site, Sorafenib, Liver Diseases, Digestive System Neoplasms