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

Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00335829
• Other study ID #: J0598 CDR0000483104
• Secondary ID: JHOC-J0598JHOC-N
• Status: Completed
• Phase: Phase 2
• Start date: May 2006
• Est. completion date: February 2011

Study information

• Verified date: August 2021
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Cancer
• Liver Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• chemotherapy

• embolization therapy

Procedure:
• hepatic artery infusion

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	National Cancer Institute (NCI), Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	TTP of Nontargeted Lesions Within the Liver	TTP of nontargeted lesions assessed via Kaplan-Meier methodology.	1 year
Secondary	Overall TTP	Overall TTP assessed via Kaplan-Meier methodology.	1 year
Secondary	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
Secondary	Overall Survival (OS)	OS assessed via Kaplan-Meier methodology both from initiation of therapy and from the date of diagnosis until death.	1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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