Adjuvant Therapy With Thalidomide for Chemoembolization in Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Chemoembolization (TACE) is used in the majority of advanced hepatocellular carcinomas. Randomized clinical trials indicated that TACE improves overall survival in patients with good liver function (Child-pugh A or B). However, the shortcoming of TACE is obvious: hypoxia induced neoangiogenesis after blockage of blood supply of the tumor; repeat TACE deteriorates liver cirrhosis due to toxicity of chemotherapeutic agent to the parenchyma liver. Thalidomide has been reported to have antiangiogenic and antimetastatic effects. The objectives of adjuvant therapy with thalidomide for chemoembolization is to evaluate overall survival and time to progression.

Official Title
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Phase Ⅲ Study of Adjuvant Therapy With Thalidomide for Chemoembolization in Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Thalidomide
* Drug: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatocellular carcinoma confirmed with pathology or identified with radiological images with typical features Age ≥ 18 years and ≤ 80 years At least one tumor nodule with one uni-dimension of ≥ 2 cm Child-Pugh Class A or B Total bilirubin ≤ 1.5 x upper limit of normal ALT and AST ≤ 2.0 x the upper limit of normal PT-INR<2.3,PTT < 1.5 x upper limit of normal Serum creatinine ≤ 1.5x upper limit of normal Peripheral white blood cell count of or more than 3×10(9)/L Peripheral platelet of or more than 50×10(9)/L Expected survival time not less than 3 months ECOG score 0-2 Exclusion Criteria: Tumor thrombi in main branch of portal vein Tumor involvement more than 70% of whole liver With extrahepatic metastasis Prior systemic chemotherapy or chemoembolization Congestive heart failure > NYHA class 2 History of HIV infection Active clinically serious infections (> 2 NCI-CTC Version 3.0) Recurrence of HCC after liver transplantation Pregnant or breast-feeding Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in this study Known or suspected allergy to any agent given in association with this trial Patients unable to swallow oral medication Inclined to thrombosis Inclined to hemorrhage or active hemorrhage with 1 month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide and TACE<br>Thalidomide is used for adjuvant therapy for TACE | Drug: Thalidomide<br>* Thalidomide is used for adjuvant therapy for TACE Thalidomide will be given at the dose of 200 mg/day in beginning, with dose escalation of 100 mg/day each week, until to the dosage of 400 mg/day.<br>Drug: TACE<br>* TACE (5-FU 1.0 g, OXP 150mg, MMC 10 mg, lipiodol 5-30 ml) will be performed every two months (defined as a course) until no radiological evidence of survival of tumor (based on contrast MRI) or 6 courses.<br>|
| Active Comparator: TACE only<br> | Drug: TACE<br>* TACE (5-FU 1.0 g, OXP 150mg, MMC 10 mg, lipiodol 5-30 ml) will be performed every two months (defined as a course) until no radiological evidence of survival of tumor (based on contrast MRI) or 6 courses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | primary outcome is defined as overall survival. overall survival is calculated from the time of undergo treatment (TACE) to time of patients death. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression | time to progression is defined as from the time of treatment (TACE) to the time of patient's progression. the progression is defined as disease progression based on RECIST criteria. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, thalidomide, TACE, Child-Pugh Class A or B