Chemoembolization With or Without Stereotactic Body Radiosurgery for Liver Cancer

Study Overview
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Brief Summary
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This is a randomized, open-label, active comparator-controlled trial of subjects with advanced (Barcelona stage B/C) hepatocellular carcinoma. Subjects will be receive one treatment with Trans-Arterial Chemo-Embolization (TACE) prior to randomization. Subsequently, subjects will be randomized to observation or, if indicated, up to an additional TACE treatments, or to Stereotactic Body Radiotherapy (SBRT). Tumor response following interventions will be evaluated at three months.

Official Title
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Trans-Arterial Chemo-Embolization (TACE) Vs. TACE Plus Stereotactic Body Radiosurgery (SBRT) in the Treatment of Hepatocellular Carcinoma (HCC)

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Procedure: Transarterial Chemoembolization (TACE)
* Radiation: TACE+Stereotactic Body Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatocellular carcinoma (Barcelona Stage B or C) Treatment with Stereotactic Body Radiosurgery can occur within 6 weeks of enrollment Age ≥ 18 years and ≤ 70 years Eastern Cooperative Oncology Group Performance status ≤ 2 Patient has a) Radiographic enhancing liver lesions with early wash out on triple phase CT or MRI or b) histological confirmation of HCC as determined by the Liver Tumor Board Hemoglobin > 10.0 g/dL Total bilirubin > 3.0 mg/dL AST (SGOT) ≤ 3x institutional upper limit of normal ALT (SGPT) ≤ 3x institutional upper limit of normal Absolute neutrophil count ≥ 1,500/μl Platelet count ≥ 50,000/μl (may be post-transfusion if clinically indicated) Aggregate maximal dimension of liver tumors ≤ 8 cm Cirrhosis classified as Child Pugh Class A or B (score ≤ 7) Determined by the treating physician to be medically eligible for liver transplantation measured by imaging modality (MRI/CT scan) three months post final treatment Life expectancy ≥ 12 weeks Ability to understand study and provide legally effective written informed consent Women of child-bearing potential must have a negative test within 4 weeks to the start of the SBRT treatment and must not be pregnant or nursing a child Sexually active women must agree to use accepted forms of birth control throughout the study, which include abstinence, oral contraceptives (birth control pills), IUD, diaphragm with spermicide, Norplant, hormone injections, condoms with spermicide, or documentation of medical sterilization Exclusion Criteria: History of abdominal radiation Cirrhosis classified as Child Pugh Class B with score ≥ 8 Prior invasive malignancy other than primary liver malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years Evidence of metastatic disease prior to registration Evidence of main portal vein thrombosis History of cardiac ischemia or stroke within 6 months prior to enrollment Any concurrent medical or psychosocial condition that prohibits a major surgical procedure or immunosuppressant that would constitute a contraindication to liver transplantation History of sorafenib therapy within 21 days prior to enrollment

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transarterial Chemoembolization (TACE)<br>Subjects will randomized receive one TACE treatment then receive observation or up to 3 additional TACE treatments as clinically indicated. | Procedure: Transarterial Chemoembolization (TACE)<br>* TACE is a treatment modality where local delivery of an anti-neoplastic agent is performed through the feeding artery of the tumor followed by end embolization of the artery. The goal of TACE is to cause tumor necrosis and tumor control via acute arterial occlusion while preserving as much functional liver tissue as possible.<br>|
| Experimental: TACE+Stereotactic Body Radiotherapy<br>Subjects will receive one TACE treatment then receive 1-5 Stereotactic Body Radiotherapy treatments. | Procedure: Transarterial Chemoembolization (TACE)<br>* TACE is a treatment modality where local delivery of an anti-neoplastic agent is performed through the feeding artery of the tumor followed by end embolization of the artery. The goal of TACE is to cause tumor necrosis and tumor control via acute arterial occlusion while preserving as much functional liver tissue as possible.<br>Radiation: TACE+Stereotactic Body Radiotherapy<br>* This intervention adds Stereotactic Body Radiation (SBRT) to TACE therapy. SBRT is the precise administration of large doses of radiotherapy delivered over 1-5 treatments to extra-cranial tumors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate | Tumor Response Rate of stage B or C Hepatocellular Carcinoma using TACE vs. TACE plus SBRT at 3 months | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor down staging | Incidence of down staging of stage B or C Hepatocellular Carcinoma using TACE plus SBRT when compared to TACE at 3 and 6 months | 3 and 6 months | 
| Frequency of adverse events | Incidence of Grade 3 or 4 adverse events associated with SBRT for liver tumors | 6 months | 
| Incidence of local tumor progression | Incidence of local progression as demonstrated by radiological imaging (RECIST criteria) | 6 months | 
| Number of patients eligibility for liver transplantation | Number of patients achieving sufficient tumor response to attain eligibility for liver transplantation. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Chemoembolization