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

Sponsor

Gachon University Gil Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT03008512

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

2.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: Genexol-PM	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2016

Actual Primary Completion Date :

Feb 1, 2021

Actual Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Genexol-PM 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 Other Names: Cremophor-free, polymeric micelle-formulated paclitaxel

Arm

Intervention/Treatment

Experimental: Genexol-PM

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

Other Names:

Cremophor-free, polymeric micelle-formulated paclitaxel

Outcome Measures

Primary Outcome Measures

Progression-free survival rate at 6 months [Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)]

Secondary Outcome Measures

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 [Cycle 1 through Follow Up (Approximately 12 Months)]
NCI-CTCAE V4.03

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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