Bevacizumab and Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying chemotherapy drugs directly into the tumor and blocking the blood flow to the tumor. Giving bevacizumab together with chemoembolization may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with chemoembolization works in treating patients with liver cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Improve median progression-free survival of patients with unresectable hepatocellular cancer treated with bevacizumab and transarterial chemoembolization therapy. Secondary Characterize the safety and toxicity of this regimen in these patients. Determine the response rate in patients treated with this regimen. OUTLINE: Patients receive bevacizumab once in weeks 1, 3, and 5. Beginning in week 3, patients also receive transarterial chemoembolization (TACE) therapy. Treatment repeats approximately every 8 weeks for up to 3 courses. Patients achieving < 100% necrosis by MRI after the first course receive 2 additional courses of bevacizumab and TACE. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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Phase II Trial of Bevacizumab Combined With Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: chemotherapy
* Drug: embolization therapy
* Procedure: hepatic artery infusion


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed* hepatocellular carcinoma Unresectable disease Child's class A or B with liver-predominant and asymptomatic extrahepatic disease NOTE: *A highly suspicious liver mass on CT scan or MRI in the presence of alpha fetoprotein > 200 mg/dL may be used as alternative diagnostic criterion PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count > 1,500/mm³ Platelet count > 50,000/mm³ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 times upper limit of normal (ULN) Bilirubin ≤ 5.0 mg/dL Creatinine normal OR creatinine clearance > 50 mL/min No significant traumatic injury within the past 28 days No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No serious, nonhealing wound, ulcer, or bone fracture PRIOR CONCURRENT THERAPY: No major surgery or open biopsy within the past 28 days No minor surgery (e.g., fine-needle aspirations or core biopsies) within the past 7 days No chemotherapy within the past 4 weeks No radiotherapy within the past 21 days No concurrent major surgery No other concurrent chemotherapy No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm, received bevacizumab and TACE<br> | Biological: bevacizumab<br> <br> Drug: chemotherapy<br> <br> Drug: embolization therapy<br> <br> Procedure: hepatic artery infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-free Survival | This outcome was not assessed. Instead, the primary outcome of time to tumor progression (TTP) of the targeted lesions and secondary outcomes of TTP of nontargeted lesions and overall TTP were assessed and reported. | Time through study completion, an average of 1 year | 
| Time to Tumor Progression (TTP) of Targeted Lesions | Time to tumor progression was estimated via Kaplan-Meier methodology using the 23 patients who underwent treatment. | 6 months and 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTP of Nontargeted Lesions Within the Liver | TTP of nontargeted lesions assessed via Kaplan-Meier methodology. | 1 year | 
| Overall TTP | Overall TTP assessed via Kaplan-Meier methodology. | 1 year | 
| TTP Rate at 6 Months and 1 Year | Overall TTP assessed via Kaplan-Meier methodology at 6 months and 1 year | 6 months and 1 year | 
| Overall Survival (OS) | OS assessed via Kaplan-Meier methodology both from initiation of therapy and from the date of diagnosis until death. | 1 year | 
| Response Rate - Based on Response Evaluation Criteria in Solid Tumors (RECIST) | Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, 3 weeks after TACE, and 4 weeks after completion of final cycle. Complete Response (CR): Disappearance of all lesions targeted by therapy Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by therapy Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by therapy Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD. | 6 months | 
| Response Rate - Based on Tumor Enhancement | Efficacy as assessed by radiographic tumor response utilizing the following tumor enhancement criteria: Complete Response (CR): 100% tumor necrosis of the target lesion(s) upon completion of any of the 3 cycles of TACE therapy Partial Response (PR): Greater than 50% tumor necrosis of target lesion(s) Progressive Disease (PD): Reappearance or increased tumor enhancement greater than 25% in target lesion(s) Stable Disease (SD): Cases that do not meet CR or PR and did not demonstrate evidence of tumor progression. | 6 months | 
| Safety and Treatment Toxicity - Cycle 1 Pre-TACE | Safety and toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0) for all patients (n=26) who received bevacizumab prior to TACE therapy. | Cycle 1 pre-TACE - 2 weeks | 
| Safety and Treatment Toxicity - Cycle 1 Post-TACE | Safety and toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0) for 25 who completed the first cycle of TACE and bevacizumab therapy | Cycle 1 post-TACE - 5 weeks | 
| Safety and Treatment Toxicity - Cycles 2 and 3 | Safety and toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0) for patients (n=14) who completed 2 or 3 cycles of TACE and bevacizumab therapy | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized unresectable adult primary liver cancer, adult primary hepatocellular carcinoma, advanced adult primary liver cancer, recurrent adult primary liver cancer