A Study of Tarceva (Erlotinib) and Avastin (Bevacizumab) in Patients With Advanced or Metastatic Liver Cancer.

Study Overview
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Brief Summary
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This single arm study evaluated the efficacy and safety of a combination of Tarceva and Avastin in patients with advanced or metastatic liver cancer. Patients were treated with Tarceva 150 mg po daily plus Avastin 5 mg/kg intravenous (iv) every 2 weeks. The anticipated time on study treatment was until disease progression, and the target sample size was <100 individuals.

Official Title
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A Single Arm, Open Label Study of First Line Treatment With Tarceva Plus Avastin on Progression-free Survival in Patients With Advanced or Metastatic Liver Cancer

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: bevacizumab (Avastin)
* Drug: erlotinib (Tarceva)


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, not previously treated with local therapy within 4 weeks of enrollment. Exclusion Criteria: prior or concomitant systemic anti-cancer treatment for advanced disease; patients at high risk of variceal bleeding; clinically significant cardiovascular disease; major surgery, open biopsy, or significant traumatic injury within 4 weeks of study start.

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: bevacizumab + erlotinib<br>Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity. | Drug: bevacizumab (Avastin)<br>* 5 mg/kg iv on day 1 of each 2 week cycle.<br>Drug: erlotinib (Tarceva)<br>* 150 mg orally (po) daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression-free Survival (PFS) | Percentage of participants who were alive and without documented progressive disease 16 weeks after their first dose of study drug. Diagnosis of Progressive Disease was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR). Analysis of tumor response was based on the best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST), which was defined as the best response recorded from the start of trial treatment until disease progression/recurrence (or death), taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. PD required at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Event driven (median follow-up 12 months) | 
| Disease Control Rate (DCR) | Disease Control Rate was defined as the percentage of participants with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 8 weeks by Response Evaluation Criteria in Solid Tumours (RECIST). CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; for non-target lesions persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits. | Event driven (median follow-up 12 months) | 
| Time to Tumor Progression | Time to tumor progression was defined as the time period in months from the start of study drug treatment to disease progression. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Event driven (median follow-up 12 months) | 
| Progression-free Survival (PFS) | PFS was defined as the time period in months from the start of study drug treatment to the first of either progression or death. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Event driven (median follow-up 12 months) | 
| Overall Survival (OS) | OS was defined as the time period in months from the start of study drug treatment to death. | Event driven (median follow-up 12 months) | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. | Up to 107 Weeks |