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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Lipotecan® (TLC388)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lipotecan® (TLC388)<br>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)<br>* 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 Ax: TLC388 MTD x 6 dose + 3DCRT<br>* Other names: Lipotecan (TLC388);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, PVTT