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

Primary Purpose

Carcinoma, Hepatocellular

Status

Terminated

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Genexol-PM

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Liver Neoplasms, Antineoplastic Agents, Carcinoma, Hepatocellular, Genexol-PM, Neoplasms by Site, Sorafenib, Liver Diseases, Digestive System Neoplasms

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
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
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:

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

Sites / Locations

Gachon University Gil Medical Center
Samsung Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Genexol-PM

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression-free survival rate at 6 months

Secondary Outcome Measures

Progression-free survival

Overall survival

Objective response rate

Adverse events

NCI-CTCAE V4.03

Full Information

NCT ID

NCT03008512

First Posted

December 29, 2016

Last Updated

February 2, 2021

Sponsor

Gachon University Gil Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03008512

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Terminated

Why Stopped

Poor accrual

Study Start Date

October 2016 (Actual)

Primary Completion Date

February 2021 (Actual)

Study Completion Date

February 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Gachon University Gil Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Hepatocellular

Keywords

Liver Neoplasms, Antineoplastic Agents, Carcinoma, Hepatocellular, Genexol-PM, Neoplasms by Site, Sorafenib, Liver Diseases, Digestive System Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Genexol-PM

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Genexol-PM

Other Intervention Name(s)

Cremophor-free, polymeric micelle-formulated paclitaxel

Primary Outcome Measure Information:

Title

Progression-free survival rate at 6 months

Time Frame

Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)

Secondary Outcome Measure Information:

Title

Progression-free survival

Time Frame

Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)

Title

Overall survival

Time Frame

Baseline to Death from Any Cause (Approximately 12 Months)

Title

Objective response rate

Time Frame

Baseline to Objective Progression (Approximately 12 Months)

Title

Adverse events

Description

NCI-CTCAE V4.03

Time Frame

Cycle 1 through Follow Up (Approximately 12 Months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dong Bok Shin, Professor

Organizational Affiliation

Gachon University Gil Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Gachon University Gil Medical Center

City

Incheon

Country

Korea, Republic of

Facility Name

Samsung Medical Center

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

15173077

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. doi: 10.1158/1078-0432.CCR-03-0655.

Results Reference

background

PubMed Identifier

9849493

Citation

Strumberg D, Erhard J, Harstrick A, Klaassen U, Muller 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. doi: 10.1016/s0959-8049(98)00054-9.

Results Reference

background

PubMed Identifier

23389639

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.

Results Reference

background

PubMed Identifier

20683437

Citation

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.

Results Reference

background

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

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