A Dose-escalation Study of Lipotecan® Plus Radiotherapy in Locally Advanced Hepatocellular Carcinoma

Phase 1

Terminated

• Conditions: Carcinoma, Hepatocellular
• Interventions: Drug: Lipotecan® (TLC388)

• Registration Number: NCT01425996
• Lead Sponsor: Taiwan Liposome Company

Brief Summary

Radiotherapy (R/T) for locally advanced hepatocellular carcinoma (HCC) is often used in patient who is not suitable for transarterial chemoembolization (TACE) and other local therapy, especially in those with portal vein tumor thrombosis (PVTT) caused by tumor cells. Several previous studies have showed that local R/T is tolerable and can induce a substantial tumor response in HCC management. In addition, the safety, toxicity and preliminary efficacy of Lipotecan® (TLC388) has also been proved in patients with terminal malignancy. This study aims to evaluate the safety, tolerability and efficacy of concomitant Lipotecan® and radiotherapy in patients with locally advanced HCC and PVTT.

Detailed Description

Lipotecan® is a drug product of TLC388 HCl, which is a potent camptothecin analog with cytotoxic activities against a variety of human tumor cell lines and anti-tumor activities in several xenograft models with human tumor cell lines. Structurally, TLC388 HCl is related to other camptothecins, but it has been chemically modified to improve stability and potency, and to minimize toxicities.

Study Timeline

• Study First Submitted: 2011-08-15
• Study First Submitted QC: 2011-08-29
• Study First Posted: 2011-08-30
• Study Start: 2011-10-27
• Primary Completion: 2014-10-03
• Study Completion: 2014-10-03
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-20
• Last Update Posted: 2018-08-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• Females or males 20-70 years of age (inclusive)
• Patients with histological confirmed HCC or other conditions
• Patients with locally advanced HCC and PVTT that is not suitable for other local therapies
• Other inclusion criteria also apply

Exclusion Criteria

• Females who are pregnant/lactating or planning to be pregnant, or patients of childbearing potential who are not using medically recognized method of contraception.
• Patients with documented extrahepatic metastasis
• Patients with stage III-IV encephalopathy or tense ascites
• Patients who have received any local or systemic therapy for HCC within 4 weeks prior to the initiation of study treatment
• Patients who have received Lipotecan® treatment prior to the initiation of study treatment
• Other exclusion criteria also apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Lipotecan® (TLC388)	Lipotecan® (TLC388)	Dosage form: 40mg TLC388 base/vial lyophilized cake Dose: Chemotherapy, i.v. q.w. x 6 doses (dose-escalation) \* The dosage regimen would be escalated gradually until MTD had been found out.

Primary Outcome Measures

Name	Time	Method
Adverse Event/Serious Adverse Event	week 12	Serious/ Adverse Event
PVTT response rate	week7	PVTT response rate
Maximum tolerated dose (MTD)	week 12	Maximum tolerated dose
Dose-limiting toxicity (DLT)	week 12	Dose-limiting toxicity

Secondary Outcome Measures

Name	Time	Method
Tumor downstaging rate	week7, week12	Tumor downstaging rate
Progression-free survival (PFS)	week7, week12, 1 year	Progression-free survial
Hepatic tumor response rate (overall tumor response rate)	week7, week12	Hepatic tumor response rate (overall tumor response rate)
Change from baseline in tumor marker/biomarkers	week4, week7, week12	Change from baseline in tumor marker/biomarkers
Overall survival (OS)	week7, week12, 1year	Overall survival
Time to progression (TTP)	week7, week12, 1 year	Time to progression

Trial Locations

Locations (2)

Taipei Veteran General Hospital; 🇨🇳 Taipei, Taiwan

Mackay Memorial Hospital; 🇨🇳 Taipei, Taiwan