A Study of Avastin (Bevacizumab) and Xeloda (Capecitabine) in Patients With Advanced or Metastatic Liver Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of oral Xeloda (capecitabine) plus intravenous Avastin (bevacizumab) in patients with advanced or metastatic liver cancer. The anticipated time on study treatment is 3-12 months.

Official Title
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A Single-arm, Open-label Study of Avastin Plus Xeloda on Objective Treatment Response in Patients With Advanced or Metastatic Liver Cancer Who Have Had no Previous Cytotoxic Chemotherapy

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: capecitabine [Xeloda]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; advanced or metastatic liver cancer; >=1 measurable lesion. Exclusion Criteria: current radiotherapy, chemotherapy, or other experimental therapies; prior cytotoxic chemotherapy; major surgery, open biopsy, or traumatic injury within 28 days of study entry; history of a malignancy during the last 5 years, other than cutaneous basal cell cancer or in situ cervical cancer.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avastin + Xeloda<br> | Drug: bevacizumab [Avastin]<br>* 7.5mg/kg iv on day 1 of each 3 week cycle.<br>Drug: capecitabine [Xeloda]<br>* 1600mg/m2/day po in 2 divided doses, on days 1 to 14 of each 3 week cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. The best overall response achieved within the time from first drug administration to progressive disease or end of study was reported. CR was defined as complete disappearance of all target lesions and non-target disease, with the normalization of tumor marker levels. No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target lesions. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker levels above the normal limits. No new lesions. | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Control | The percentage of participants with disease control was based on assessment of confirmed CR, PR, or stable disease (SD) according to RECIST criteria. Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. The best overall response achieved within the time from first drug administration to progressive disease or end of study was reported. CR was defined as complete disappearance of all target lesions and non-target disease, with the normalization of tumor marker levels. No new lesions. PR was defined as ≥ 30 % decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target lesions. Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker levels above the normal limits. No new lesions. SD was defined as not qualifying for PR or progressive disease. | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | 
| Time to Disease Progression - Percentage of Participants With an Event | Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of last tumor assessment. | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | 
| Time to Disease Progression | Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of their tumor assessment. | Screening; Weeks 6, 12, 18, 24, and 30; Every 3 months through follow-up | 
| Time to Disease Progression - Percentage of Participants Progression-free at 12 Months | Time to progression was measured from time of treatment commencement to time of disease progression, or the date of death. Participants who were not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the date of last tumor assessment. | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | 
| Overall Survival - Percentage of Participants With an Event | Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | 
| Overall Survival | Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. Median Overall Survival was estimated using the Kaplan-Meier method. | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. | 
| Overall Survival - Percentage of Participants Event Free at 12 Months | Overall Survival was defined as the time in months from randomization to date of death due to any cause. Participants without an event were censored the last time they were known to be alive. | Day 1, Weeks 1-18, Weeks 24 and 30, then every 3 months until death. |