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

A Phase I/II, Dose-escalation Study of Lipotecan® Plus Radiotherapy in Locally Advanced Hepatocellular Carcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Lipotecan® (TLC388)

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Mackay Memorial Hospital
  • Taipei, Taiwan
    • Taipei Veteran General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Lipotecan® (TLC388); Cohort A1: TLC388 15 mg/m2 x 6 dose + 3DCRT; Cohort A2: TLC388 30 mg/m2 x 6 dose + 3DCRT; Cohort A3: TLC388 40 mg/m2 x 6 dose + 3DCRT; Cohort A4: TLC388 50 mg/m2 x 6 dose + 3DCRT (dose-escalation); Cohort A"x": TLC388 "MTD" x 6 dose + 3DCRT; Other Names: Lipotecan (TLC388)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Maximum tolerated dose	week 12
PVTT response rate	PVTT response rate	week7
Dose-limiting toxicity (DLT)	Dose-limiting toxicity	week 12
Adverse Event/Serious Adverse Event	Serious/ Adverse Event	week 12

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Principal Investigator: Tsang-En Wa, MD, Mackay Memorial Hospital; Principal Investigator: Yee Chao, MD, Taipei Veteran General Hospital; Principal Investigator: Chen-Hsi Hsieh, MD, Far Eastern Memorial Hospital; Principal Investigator: Jacqueline Whang-Peng, MD, Wan Fang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2011
• Primary Completion (Actual): October 3, 2014
• Study Completion (Actual): October 3, 2014

Study Registration Dates

• First Submitted: August 15, 2011
• First Submitted That Met QC Criteria: August 29, 2011
• First Posted (Estimate): August 30, 2011

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: HCC; PVTT
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Camptothecin
• Other Study ID Numbers: TLC388.2