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

Phase 2

Terminated

• Conditions: Carcinoma, Hepatocellular
• Interventions: Drug: Genexol-PM

• Registration Number: NCT03008512
• Lead Sponsor: Gachon University Gil Medical Center

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.

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 Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-12-29
• Study First Submitted QC: 2016-12-29
• Study First Posted: 2017-01-02
• Status Verified: 2021-02
• Primary Completion: 2021-02
• Study Completion: 2021-02
• Last Update Submitted: 2021-02-02
• Last Update Posted: 2021-02-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

1. A diagnosis of hepatocellular carcinoma (HCC) based on either

   1. histopathologic or cytologic findings
   2. 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)

2. Previous sorafenib treatment for at least 14 days and discontinuation of sorafenib treatment prior to inclusion

3. Radiologic confirmation of disease progression during or after discontinuation of sorafenib treatment or discontinuation of sorafenib due to intolerance despite appropriate supportive care

4. Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B disease not amenable to locoregional therapy or refractory to locoregional therapy

5. ≥ 1 measurable lesion according to RECIST Version 1.1

6. ≥ 20 year of age

7. ECOG performance status ≤ 2

8. Child-Pugh score ≤ 7

9. Informed consent prior to study

10. Adequate organ function

    1. Hepatic: bilirubin ≤ 1.5 times upper limit of institutional normal value (ULN), AST or ALT ≤ 5 x ULN
    2. Renal: estimated creatinine clearance ≥ 60 mL/min
    3. 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.)
    4. Coagulation: prothrombin time (INR) ≤ 1.5, partial thrombin time (PTT) ≤ 5 seconds above the ULN

Exclusion Criteria

1. Previous systemic chemotherapy for advanced disease (except previous biologic agents including VEGF inhibitors, TGF-beta inhibitors, or PD-1/PD-L1 blockers)
2. A history o f or current hepatic encephalopathy or clinically meaningful ascites
3. Grade 2 or more peripheral neuropathy
4. Prior liver transplant
5. 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.)
6. A history of treatment with taxanes (paclitaxel or docetaxel)
7. Females who are pregnant or lactating
8. A know allergy or hypersensitivity reaction to any of the treatment components
9. Serious preexisting medical conditions that cannot adequately controlled with appropriate therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Genexol-PM	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of