Phase II Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer (HCC)
Overview
- Phase
- Phase 2
- Intervention
- bevacizumab
- Conditions
- Adult Primary Hepatocellular Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR).
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with advanced liver cancer. 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. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and erlotinib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with erlotinib may kill more tumor cells
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate the objective response rate in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib. SECONDARY OBJECTIVES: I. Evaluate the time to progression in patients treated with this regimen. II. Evaluate the overall and progression-free survival of patients treated with this regimen. III. Evaluate the adverse events in patients treated with this regimen. TERTIARY OBJECTIVES: I. Determine the presence of epidermal growth factor receptor (EGFR) mutations in tumor tissue and correlate this with response rate, progression, and survival in patients treated with this regimen. II. Evaluate the expression of molecules involved in EGFR signal transduction, including EGFR, phosphorylated-EGFR, Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK), phosphorylated-MAPK, and HER2/neu by immunohistochemistry (from tumor tissue) and correlate these with patient outcome measures. III. Determine the levels of vascular endothelial growth factor (VEGF) and VEGF receptors in tumor tissue as well as baseline plasma VEGF levels and correlate these with patient outcome measures. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine epidermal growth factor receptor (EGFR) and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by immunohistochemistry (IHC) for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK), and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by enzyme-linked immunosorbent assays (ELISA). After completion of study treatment, patients are followed periodically for up to 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Absolute neutrophil count \>= 1,500/mm\^3
- •Creatinine =\< 2 mg/dL
- •Albumin \>= 2.5 g/dL
- •Total bilirubin =\< upper limit of normal (ULN)
- •aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times ULN
- •Alkaline phosphatase =\< 5 times ULN
- •Urine protein:creatinine ratio \< 1.0 OR 24-hour urine protein \< 1,000 mg
- •Not pregnant or nursing:
- •No nursing for \>= 6 months after completion of study treatment
- •Negative pregnancy test
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (monoclonal antibody, enzyme inhibitor)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
Intervention: bevacizumab
Treatment (monoclonal antibody, enzyme inhibitor)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.
Intervention: erlotinib hydrochloride
Outcomes
Primary Outcomes
Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR).
Time Frame: Patients were able to continue treatment indefinitely and were evaluated every cycle until discontinued treatment.
Responses to erlotinib and bevacizumab treatment were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters.
Secondary Outcomes
- Survival Time(From registration to death due to any cause, patients are followed up to 3 years after treatment)
- Duration of Response(The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.)
- Time to Treatment Failure(From the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal.)
- Time to Disease Progression(From registration to documentation of disease progression, up to 3 years after treatment.)