Carcinoma, Hepatocellular
Conditions
Keywords
HCC, PVTT
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.
Interventions
DRUGLipotecan® (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 Ax: TLC388 MTD x 6 dose + 3DCRT
Sponsors
Taiwan Liposome Company
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | week 12 | Maximum tolerated dose |
| PVTT response rate | week7 | PVTT response rate |
| Dose-limiting toxicity (DLT) | week 12 | Dose-limiting toxicity |
| Adverse Event/Serious Adverse Event | week 12 | Serious/ Adverse Event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | week7, week12, 1year | Overall survival |
| 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 |
| Tumor downstaging rate | week7, week12 | Tumor downstaging rate |
| Time to progression (TTP) | week7, week12, 1 year | Time to progression |
| Progression-free survival (PFS) | week7, week12, 1 year | Progression-free survial |
Countries
Taiwan
Outcome results
None listed