Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis

Primary objective: To evaluate the safety and tolerability, including maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), of Lipotecan based concurrent chemoradiotherapy (CCRT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) unsuitable for local treatment. Secondary Objective: The secondary objective is to explore the efficacy of Lipotecan based CCRT in patients with HCC and PVTT and the effect on quality of life.

Lipotecan®; (TLC388 HCl for Injection)

TLC388 HCl

Injection

40

Primary Outcome Measures :
Maximum tolerated dose determination for Lipotecan based CCRT [ Time Frame: 3 months ]
To determine maximum tolerated dose for Lipotecan based CCRT in HCC patients with portal vein tumor thrombosis

Best objective response evaluation of portal vein tumor thrombosis [ Time Frame: 1 year ]
To evaluate the best objective response rate of portal vein tumor thrombosis


Secondary Outcome Measures :
Conversion rate (CR) of portal vein tumor thrombosis [ Time Frame: 1 year ]
To evaluate the conversion rate (CR rate) of PVTT

Best overall response of overall disease [ Time Frame: 1 year ]
To evaluate the best overall response rate of overall disease

Disease control rate of portal vein tumor thrombosis, liver tumors and overall disease [ Time Frame: 1 year ]
To evaluate DCR of PVTT, liver tumors (target lesions), and overall disease

Time to progression of overall disease [ Time Frame: 1 year ]
To evaluate the TTP of overall disease after the start of concomitant Lipotecan based CCRT

Progression free survival of overall disease [ Time Frame: 1 year ]
To evaluate the PFS of overall disease after the start of concomitant Lipotecan based CCRT

Overall survival of overall disease [ Time Frame: 1 year ]
To evaluate the OS after the start of concomitant Lipotecan based CCRT

Inclusion Criteria:
1. Patients will be males or females
o ≥20 years of age in Taiwan
o ≥18 years old in China
2. Patients with histologically confirmed HCC or patients who do not have histological diagnosis, but the lesion is larger than 1 cm in a cirrhotic liver with typical HCC image of contrast enhanced CT scan or MRI. If the image characteristic is not typical of HCC, another contrast enhanced image modality should be confirmed for diagnosis.
3. Patients with PVTT (BCLC stage C) who are not suitable for local therapies
4. Patients with a measureable targeting lesion
5. Patients with an anticipated residual life expectancy ≥3 months
6. Patients who have adequate organ function
7. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2
8. Patients who are willing to follow birth control requirements during the study treatment and continue until 2 months after the completion of study treatment
9. Patients willing and able to comply with the study procedures and to sign a written ICF

Exclusion Criteria:
1. Patients with infiltrative type HCC
2. Patients with evidence of any extrahepatic metastasis, including but not limited to inferior vena cava thrombosis, bone metastasis, brain metastasis, or regional lymph node metastasis
3. Patients with a history of West Haven criteria grade III-IV hepatic encephalopathy or ascites
4. Patients with a history of other malignancy except primary HCC within 3 years prior to the screening visit, excluding skin squamous cell carcinoma or basal cell carcinoma
5. Patients who fail to follow the radiation dose constraint in any critical organ in the radiotherapy planning
6. Patients with an inadequately defined hepatic tumor margin for RT planning on MRI or CT that may impact treatment or safety based on investigator's judgment
7. Patients who have experienced significant allergy or hypersensitivity to the contrast medium for CT or MRI that makes it unsafe to perform the delineation for RT planning
8. Patients with a history of liver transplantation
9. Patients with a significant concurrent disease