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Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lipotecan
Sponsored by
Taiwan Liposome Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

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

Inclusion Criteria:

  • Radiological diagnosis of hepatic tumor(s) by contrast-enhanced study
  • Subjects with advanced HCC who are not eligible for surgical resection or loco-regional therapy.
  • Subjects with sorafenib treatment failure due to sorafenib intolerance or radiographic PD (as per RECIST v1.1). Prior sorafenib use should be ≥ 400 mg/day for at least 14 days.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
  • Child Pugh Score ≤ 6;
  • A life expectancy of at least 12 weeks or more

Exclusion Criteria:

  • Subjects who have received any systemic target therapy or systemic chemotherapy other than sorafenib for the treatment of HCC.
  • Subjects who have received sorafenib within 2 weeks prior to the initiation of the treatment dose, or have any sorafenib-related toxicities not yet resolved to grade 1 or baseline.
  • Subjects who have undergone liver transplantation surgery.
  • Major surgery within 4 weeks prior to the initiation of the treatment dose (excluding implantation of the intravenous infusion device). Percutaneous liver puncture within 2 weeks prior to the initiation of the treatment dose.

Sites / Locations

  • 307 Hospital of PLA
  • Nanjing Bayi Hospital
  • Shanghai Cancer Hospital, Fudan University
  • Zhongshan Hospital, Fudan University
  • Chiayi Chang Gung Memorial Hosipital
  • Kaohsiung Chang Gung Memorial Hospital
  • China Medical University Hosipital
  • National Cheng Kung University Hospital
  • Mackay Memorial Hosipital
  • National Taiwan University Hosipital
  • Taipei Veterans General Hospital
  • LinKou Chang Gung Memorial Hosipital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lipotecan

Arm Description

Administer 40mg of Lipotecan at D1, D8, D15 of each cycles.

Outcomes

Primary Outcome Measures

Disease Control Rate (DCR)
DCR (Disease control rate), the percentage of subjects with a best response rate of complete response (CR), partial response (PR), or stable disease (SD)

Secondary Outcome Measures

Objective response rate (ORR; where ORR= CR rate + PR rate)
ORR (Objective response rate)
Duration of Disease control (DDC)
Duration of disease control is defined as the time from first documented evidence of CR or PR or SD until the first documentation of PD or death due to any cause, whichever occurs first.
Time to Progression (TTP)
Time to tumor progression is defined as the time from first study drug administration until the first documentation of tumor progression.
Progression Free Survival (PFS)
The PFS is defined as the time from the first dose to the date of progression or death, whichever occurs first, and subjects with no evidence of progression or death at the time of study completion (the analysis cut-off date) or who are receiving any further anticancer therapy will be censored on the date of the last adequate tumor assessment.
Overall Survival (OS)
The OS is defined as the time from the first dose to the date of death, regardless of the cause of death, and subjects who are alive at the time of study completion will be censored at the last known alive date. Subjects who commence treatment with another anticancer agent will be censored at the day before the other anticancer treatment starts.
Change of Tumor markers/Bio-markers
tumor markers/biomarkers, including α-fetoprotein (AFP), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6)
AEs
Serious/ Adverse Events
Vital signs
evaluate at every administration and the end of treatment
Resting 12-lead ECGs
12-Lead ECGs
Hematology
evaluate at every administration and the end of treatment
Clinical chemistry
evaluate at every administration and the end of treatment
Urinalysis data
Urinalysis Lab Values
PK parameters, including AUC, Cmax and Tmax of S,S-TLC388, S,R-TLC388, metabolites TLC-U1, TLC-U2, and topotecan
PK parameters

Full Information

First Posted
September 11, 2014
Last Updated
February 23, 2019
Sponsor
Taiwan Liposome Company
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1. Study Identification

Unique Protocol Identification Number
NCT02267213
Brief Title
Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma
Official Title
An Open-Label, Single-Arm, Two-Stage, Multi-Centre Phase II Study to Evaluate the Efficacy and Safety of TLC388 as Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
Current study design couldn't support futher development on this indication
Study Start Date
April 10, 2014 (Actual)
Primary Completion Date
July 9, 2015 (Actual)
Study Completion Date
July 9, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taiwan Liposome Company

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and efficacy of TLC388 (Lipotecan) as a second line treatment in subjects with advanced Hepatocellular Carcinoma.
Detailed Description
A Phase II, open-label, single-arm, two-stage, multicenter study to evaluate the efficacy and safety of Lipotecan® monotherapy in patients with advanced hepatocellular carcinoma (HCC) and had failed sorafenib treatment due to sorafenib intolerance or radiographic progressive disease (PD). Eligible patients received 40 mg/m2 of Lipotecan®, given as a 30-minute (+3 minutes) intravenous infusion, on Days 1, 8, and 15 of a 28-day cycle for maximum 6 cycles. Inter-cycle and intra-cycle dose delays were allowed within 21 days of the scheduled date to be reduced to 35 mg/m2 and further to 30 mg/m2 if a treatment-related adverse event (TRAE) met the criteria for dose reduction. Tumor response was assessed every 2 cycles until Cycle 6, or at the early termination according to RECIST Version 1.1 judged by site investigator. The favorable response of CR, PR or SD would be confirmed within 28-35 days. Safety evaluations were conducted on a weekly basis from the day study treatment administered throughout each cycle.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lipotecan
Arm Type
Experimental
Arm Description
Administer 40mg of Lipotecan at D1, D8, D15 of each cycles.
Intervention Type
Drug
Intervention Name(s)
Lipotecan
Other Intervention Name(s)
Lipotecan, TLC388
Intervention Description
Administer 40mg Lipotecan at D1, D8, D15 of each cycle.
Primary Outcome Measure Information:
Title
Disease Control Rate (DCR)
Description
DCR (Disease control rate), the percentage of subjects with a best response rate of complete response (CR), partial response (PR), or stable disease (SD)
Time Frame
8 weeks from initial treatment
Secondary Outcome Measure Information:
Title
Objective response rate (ORR; where ORR= CR rate + PR rate)
Description
ORR (Objective response rate)
Time Frame
8 weeks(Cycle 2), 16 weeks (Cycle 4), 24 weeks (Cycle 6) from initial treatment and/or Early termination (before 24 weeks)
Title
Duration of Disease control (DDC)
Description
Duration of disease control is defined as the time from first documented evidence of CR or PR or SD until the first documentation of PD or death due to any cause, whichever occurs first.
Time Frame
2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
Title
Time to Progression (TTP)
Description
Time to tumor progression is defined as the time from first study drug administration until the first documentation of tumor progression.
Time Frame
2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
Title
Progression Free Survival (PFS)
Description
The PFS is defined as the time from the first dose to the date of progression or death, whichever occurs first, and subjects with no evidence of progression or death at the time of study completion (the analysis cut-off date) or who are receiving any further anticancer therapy will be censored on the date of the last adequate tumor assessment.
Time Frame
2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
Title
Overall Survival (OS)
Description
The OS is defined as the time from the first dose to the date of death, regardless of the cause of death, and subjects who are alive at the time of study completion will be censored at the last known alive date. Subjects who commence treatment with another anticancer agent will be censored at the day before the other anticancer treatment starts.
Time Frame
Up to 2 years from the last treatment of the last subject
Title
Change of Tumor markers/Bio-markers
Description
tumor markers/biomarkers, including α-fetoprotein (AFP), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6)
Time Frame
Baseline, the first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months)
Title
AEs
Description
Serious/ Adverse Events
Time Frame
From ICF singed to 30 days after EOT
Title
Vital signs
Description
evaluate at every administration and the end of treatment
Time Frame
Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks)
Title
Resting 12-lead ECGs
Description
12-Lead ECGs
Time Frame
Baseline, the first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months)
Title
Hematology
Description
evaluate at every administration and the end of treatment
Time Frame
Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks)
Title
Clinical chemistry
Description
evaluate at every administration and the end of treatment
Time Frame
Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks)
Title
Urinalysis data
Description
Urinalysis Lab Values
Time Frame
The first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months)
Title
PK parameters, including AUC, Cmax and Tmax of S,S-TLC388, S,R-TLC388, metabolites TLC-U1, TLC-U2, and topotecan
Description
PK parameters
Time Frame
0, 15, 29, 33, 40, 50 minutes, and 1, 1.5, 2, 4, 8 hour after the start of infusion of the 1st treatment and 1 week (2nd treatment); 0, 29 minutes and 4 hour after the start of infusion of the 3, 5, 6 and 7 weeks (the 3rd, 4th, 5th, 6th treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Radiological diagnosis of hepatic tumor(s) by contrast-enhanced study Subjects with advanced HCC who are not eligible for surgical resection or loco-regional therapy. Subjects with sorafenib treatment failure due to sorafenib intolerance or radiographic PD (as per RECIST v1.1). Prior sorafenib use should be ≥ 400 mg/day for at least 14 days. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 Child Pugh Score ≤ 6; A life expectancy of at least 12 weeks or more Exclusion Criteria: Subjects who have received any systemic target therapy or systemic chemotherapy other than sorafenib for the treatment of HCC. Subjects who have received sorafenib within 2 weeks prior to the initiation of the treatment dose, or have any sorafenib-related toxicities not yet resolved to grade 1 or baseline. Subjects who have undergone liver transplantation surgery. Major surgery within 4 weeks prior to the initiation of the treatment dose (excluding implantation of the intravenous infusion device). Percutaneous liver puncture within 2 weeks prior to the initiation of the treatment dose.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yunlong Tseng
Organizational Affiliation
Taiwan Liposome Company
Official's Role
Study Director
Facility Information:
Facility Name
307 Hospital of PLA
City
Beijin
ZIP/Postal Code
100071
Country
China
Facility Name
Nanjing Bayi Hospital
City
Nanjing
ZIP/Postal Code
210002
Country
China
Facility Name
Shanghai Cancer Hospital, Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Zhongshan Hospital, Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Chiayi Chang Gung Memorial Hosipital
City
Chiayi City
Country
Taiwan
Facility Name
Kaohsiung Chang Gung Memorial Hospital
City
Kaohsiung
Country
Taiwan
Facility Name
China Medical University Hosipital
City
Taichung
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
Country
Taiwan
Facility Name
Mackay Memorial Hosipital
City
Taipei City
Country
Taiwan
Facility Name
National Taiwan University Hosipital
City
Taipei
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
Country
Taiwan
Facility Name
LinKou Chang Gung Memorial Hosipital
City
Taoyuan
Country
Taiwan

12. IPD Sharing Statement

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Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma

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