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

Carcinoma, Hepatocellular Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03008512
• Other study ID #: weGePM-HCC
• Status: Terminated
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: February 2021

Study information

• Verified date: February 2021
• Source: Gachon University Gil Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Genexol-PM

Locations

Country	Name	City	State
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Gachon University Gil Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

Baird RD, Tan DS, Kaye SB. Weekly paclitaxel in the treatment of recurrent ovarian cancer. Nat Rev Clin Oncol. 2010 Oct;7(10):575-82. doi: 10.1038/nrclinonc.2010.120. Epub 2010 Aug 3. Review. — View Citation

Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013 Jul;16(3):481-92. doi: 10.1007/s10456-013-9334-0. Epub 2013 Feb 7. Review. — View Citation

Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, Kim NK, Bang YJ. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004 Jun 1;10(11):3708-16. — View Citation

Strumberg D, Erhard J, Harstrick A, Klaassen U, Müller C, Eberhardt W, Wilke H, Seeber S. Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma. Eur J Cancer. 1998 Jul;34(8):1290-2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival rate at 6 months		Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)
Secondary	Progression-free survival		Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)
Secondary	Overall survival		Baseline to Death from Any Cause (Approximately 12 Months)
Secondary	Objective response rate		Baseline to Objective Progression (Approximately 12 Months)
Secondary	Adverse events	NCI-CTCAE V4.03	Cycle 1 through Follow Up (Approximately 12 Months)