Safety Study of Sorafenib Following Combined Therapy of Radiation and TACE for Liver Cancer

Study Overview
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Brief Summary
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Patients with liver cancer will receive interventional therapy plus radiotherapy. Maintenance Sorafenib will be taken after the completion of radiotherapy. Hypothesis of the current study is that Sorafenib as a maintenance therapy is safe and superior to radiotherapy combined with interventional therapy in terms of survival in comparison to historical data.

Detailed Description
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Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data.

Official Title
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Maintenance of Sorafenib Following Combined Therapy of Three-dimensional Conformal Radiation Therapy/Intensity-modulated Radiation Therapy and Transcatheter Arterial Chemoembolization in Patients With Locally Advanced Hepatocellular Carcinoma: a Phase I/II Study.

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of equal or older than 18 years and not over 75 years with a life expectancy of at least 12 weeks; Karnofsky performance status (KPS) of ≥70; Histologically or cytologically confirmed HCC; BCLC stage B, solitary lesion (bigger than 5 cm in diameter) with tumor burden less than 50% of total liver volume; Liver function of Child-Pugh A; Technically unresectable, medically inoperable, or surgery declined by the patient; Normal renal function and adequate bone marrow reservation; Signed informed consent must be obtained prior to any study specific procedure. Exclusion Criteria: Presence of intrahepatic and/or extrahepatic metastases Previous received systemic therapy for liver cancer; History of radiotherapy to the liver; Indistinct tumor boundary on CT/MRI images; Previous or concurrent malignancies, with the exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix or superficial bladder tumors [Ta, Tis and T1]; History of cardiac disease: congestive heart failure > NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrhythmic therapy or uncontrolled hypertension within the last 12 months; Concurrent uncontrolled medical conditions; Pregnancy or breast feeding; Investigational drug therapy outside of this trial during or within 4 weeks of study entry; Psychiatric or medical unstable conditions that compromise the patient's ability to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sorafenib|Sorafenib is administered only to the patients with non-progression disease (CR, PR and SD) 4 weeks after the completion of radiotherapy. The dose is 400 mg, p.o., twice a day. Sorafenib is continuously given for 12 months unless intolerable toxicities and/or tumor progression.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability of maintenance Sorafenib. |  | twelve months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression (TTP), progression-free survival (PFS) and overall survival (OS) |  | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sorafenib, Three-dimensional conformal radiation therapy, Intensity-modulated radiation therapy, Transcatheter arterial chemoembolization