Clinical trial NCT02267213: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Lead sponsor: Taiwan Liposome Company
Sponsor class: INDUSTRY
First posted: 2014-10-17
Enrollment: 29
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 8 weeks from initial treatment
Secondary outcomes:
measure: Objective response rate (ORR; where ORR= CR rate + PR rate)
timeFrame: 8 weeks(Cycle 2), 16 weeks (Cycle 4), 24 weeks (Cycle 6) from initial treatment and/or Early termination (before 24 weeks)
measure: Duration of Disease control (DDC)
timeFrame: 2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
measure: Time to Progression (TTP)
timeFrame: 2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
measure: Progression Free Survival (PFS)
timeFrame: 2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
measure: Overall Survival (OS)
timeFrame: Up to 2 years from the last treatment of the last subject
measure: Change of Tumor markers/Bio-markers
timeFrame: 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)
measure: AEs
timeFrame: From ICF singed to 30 days after EOT
measure: Vital signs
timeFrame: 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)
measure: Resting 12-lead ECGs
timeFrame: 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)
measure: Hematology
timeFrame: 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)
measure: Clinical chemistry
timeFrame: 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)
measure: Urinalysis data
timeFrame: 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)
measure: PK parameters, including AUC, Cmax and Tmax of S,S-TLC388, S,R-TLC388, metabolites TLC-U1, TLC-U2, and topotecan
timeFrame: 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)
Other outcomes:
Locations:
city: Beijin
country: China
facility: 307 Hospital of PLA
city: Nanjing
country: China
facility: Nanjing Bayi Hospital
city: Shanghai
country: China
facility: Shanghai Cancer Hospital, Fudan University
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
city: Chiayi City
country: Taiwan
facility: Chiayi Chang Gung Memorial Hosipital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hosipital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Mackay Memorial Hosipital
city: Taipei
country: Taiwan
facility: National Taiwan University Hosipital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: LinKou Chang Gung Memorial Hosipital
Study officials:
affiliation: Taiwan Liposome Company
name: Yunlong Tseng
role: STUDY_DIRECTOR
References: