TACE With or Without Radiation Therapy in Treating Patients With Stage A-C Liver Cancer

Study Overview
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Brief Summary
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This randomized phase II trial studies how well transarterial chemoembolization (TACE) works compared with TACE plus radiation therapy in treating patients with end stage liver disease, liver tumors, or potential liver transplant candidates. TACE involves reaching up to the blood vessel that feeds the tumor through a catheter placed into the groin vessel. Once the physician has defined the vessel going to the tumor, chemotherapy is infused to the tumor and the vessel is blocked, maintaining the chemotherapy for longer time inside the tumor and stopping the blood flow that feeds the tumor. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that delivers radiation to the tumor cells but does not harm normal liver cells. It is not yet known whether TACE is more effective with or without SBRT in treating liver tumors.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine in patients with stage A to C hepatocellular carcinoma, if stereotactic body radiotherapy after TACE enhanced the response rate of hepatocellular carcinoma (HCC) when compared to TACE alone at 3 months. SECONDARY OBJECTIVES: I. To determine in patients with stage A to C hepatocellular carcinoma, if TACE plus SBRT can achieve a downstaging rate of >= 30% at 3 and 6 months. II. To determine the rate of grade 3 or 4 adverse events associated with SBRT for liver tumors. III. To determine the rate of local progression after SBRT. (Based on Response Evaluation Criteria in Solid Tumors [RECIST] criteria) IV. Number of patients who achieve liver transplantation. V. Overall survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms after the first loco-regional therapy with TACE. ARM I: Patients undergo TACE according to institutional standard with doxorubicin-eluting beads. ARM II: Patients undergo TACE as in Arm I and 3 or 5 fractions of SBRT given at least 48 hours apart over 14 days. After completion of study treatment, patients are followed up at 1, 3, and 6 months and then periodically thereafter.

Official Title
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Trans-Arterial Chemo-Embolization (TACE) vs TACE Plus Stereotactic Body Radio Therapy (SBRT) in the Treatment of Hepatocellular Carcinoma (HCC)

Conditions
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Adult Primary Hepatocellular Carcinoma, Recurrent Adult Primary Liver Cancer, Stage I Adult Primary Liver Cancer, Stage II Adult Primary Liver Cancer, Stage IIIA Adult Primary Liver Cancer

Intervention / Treatment
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* Procedure: transarterial chemoembolization
* Radiation: stereotactic radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC is staged as Barcelona A to C Treatment with SBRT can occur within 6 weeks of registration Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Patient has Radiographic enhancing liver lesions with early wash out on triple phase CT or MRI or Histological confirmation of HCC as determined by the Liver Tumor Board Hemoglobin greater than 10.0 g/dL Total bilirubin less than 3.0 mg/dL Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 X institutional upper limit of normal Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal Total aggregate of maximal dimension of liver tumors is =< 8 cm Cirrhotic patients Child Pugh class A or B (score =< 7) Patient must be determined by the treating physician to be medically eligible for liver transplantation measured by imaging modality (magnetic resonance imaging [MRI]/computed tomography [CT] scan) three months post final treatment Absolute neutrophil count >= 1,500/μl Platelet count >= 50,000 μl (after transfusion if required) Life expectancy > 12 weeks Subjects must have the ability to understand and be willing to provide written informed consent Women of child-bearing potential must have a negative pregnancy test within 4 weeks to the start of the SBRT treatment Women must not be pregnant or nursing Sexually active women must agree to use accepted forms of birth control; acceptable options for birth control will be documented in the consent and discussed with the subject prior to enrollment Exclusion Criteria: Patient with previous history of abdominal radiation Cirrhotic patients 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 known cardiac ischemia or stroke within last 6 months Any concurrent medical or psychosocial condition that prohibits a major surgical procedure or immunosuppression that would constitute a contraindication to liver transplantation

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: Arm I (TACE)<br>Patients undergo (transarterial chemoembolization) TACE according to institutional standard with doxorubicin-eluting beads. | Procedure: transarterial chemoembolization<br>* Undergo TACE with doxorubicin-eluting beads<br>* Other names: TACE;|
| Experimental: Arm II (TACE+SBRT)<br>Patients undergo transarterial chemoembolization (TACE) as in Arm I and 3 or 5 fractions of stereotactic radiosurgery (SBRT) given at least 48 hours apart over 14 days. | Procedure: transarterial chemoembolization<br>* Undergo TACE with doxorubicin-eluting beads<br>* Other names: TACE;Radiation: stereotactic radiosurgery<br>* Undergo SBRT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in gross tumor volume (GTV) | Percentage of tumor response as defined as change in longest diameter of tumor compared to original tumor length | Baseline to 3 months | 
| Difference in mean gross tumor volume (GTV), assessed using the RECIST method | Difference in mean GTV from T0M and T3M calculated by a student t-test | Baseline to 3 months | 
| Difference in tumor grade | Difference in the grade of tumor (as defined by the RECIST criteria) at T0 and T3 calculated using Chi-square tests. | Baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of downstaging | Rate of downstaging of stage A to C Hepatocellular Carcinoma using TACE plus SBRT when compared to TACE at 3 and 6 months. | Up to 6 months | 
| Grade 3 or 4 adverse events associated with liver tumors | Number of grade 3 or 4 adverse events associated with SBRT for liver tumors, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events | Up to 1 year | 
| Rate of local progression, based on RECIST criteria | Rate of local disease progression when progression is defined as an estimated increase of > 20% in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new lesions. | Up to 6 months | 
| Liver transplant achievement | Number of patients who achieve liver transplantation | Up to 6 months | 
| Survival rate | The number of days from the first day of treatment on study until death of any cause | 1 year |