Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is a randomized trial to evaluate the clinical benefit of sorafenib 400 mg twice daily and erlotinib 150 mg once a day versus sorafenib 400 mg twice daily and placebo erlotinib once daily in subjects with unresectable advanced or metastatic Child-Pugh A HCC. Patients who are candidates for potentially curative intervention (i.e. surgical resection or local ablation) are not eligible for this study.

Detailed Description
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European quality of life scale (5 dimensions) (EQ-5D)

Official Title
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A Phase III Randomized, Placebo Controlled, Double Blind Trial of Sorafenib Plus Erlotinib vs. Sorafenib Plus Placebo as First Line Systemic Treatment for Hepatocellular Carcinoma (HCC)

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Sorafenib (Nexavar, BAY43-9006)
* Drug: Erlotinib (Tarceva)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients > 18 years of age Patients who have a life expectancy of at least 12 weeks Patients with histological or cytologically documented HCC Patients must have at least one tumor lesion that meets both of the following criteria: The lesion can be accurately measured in at least one dimension according to response evaluation criteria in solid tumors (RECIST) The lesion has not been previously treated with local therapy Patients who have an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1 Cirrhotic status of Child-Pugh class A. Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time. Exclusion Criteria: History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin), or uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted. Abnormalities of the cornea based on history (e.g. dry eye syndrome, Sogren's syndrome) including congenital abnormality (e.g. Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g. fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test). History of interstitial lung disease (ILD). Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Previous treatment with yttrium-90 spheres Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. Uncontrolled ascites (defined as not easily controlled with diuretic treatment)

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva)<br>Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd) | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Sorafenib 400 mg twice daily<br>Drug: Erlotinib (Tarceva)<br>* Erlotinib 150 mg once daily<br>|
| Active Comparator: Sorafenib (Nexavar, BAY43-9006) + Placebo<br>Participants received sorafenib 400 mg twice daily (bid) and matching erlotinib placebo 150 mg tablet once daily (qd) | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Sorafenib 400 mg twice daily<br>Drug: Placebo<br>* Matching erlotinib placebo 150 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. | From randomization of the first patient until 34 months or date of death of any cause whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Radiological Tumor Progression (TTP) | TTP was the time from randomization to radiological tumor progression. Participants without radiological tumor progression at the time of analysis were censored at their last date of tumor evaluation. Progressive disease (PD) was defined using Response Evaluation Criteria in Solid Tumors (RECIST version 1.0), as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Appearance of new lesions also constituted PD. | From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks | 
| Disease Control | Disease control was defined as the number of participants who had a best response rating of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST assessed by magnetic resonance imaging (MRI) that was confirmed at least 28 days from the first demonstration of that rating. CR: disappearance of all clinical and radiological evidence of target and non-target tumors. PR: at least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. SD: steady state of disease. Neither sufficient shrinkage for PR nor sufficient increase for PD. | From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks | 
| Health-related Quality of Life and Utility Values as Measured by EQ-5D - Index | The European quality of life scale (5 dimensions) (EQ-5D) questionnaire was given to the participants at each visit. The EQ-5D questionnaire consisted of 5 ordinal categorical responses (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The scores for the EQ-5D dimensions are assigned according to the level of problems reported (1 'no problems'; 2 'some problems'; 3 'extreme problems'). The 5 health dimensions are summarized into a single score, the EQ-5D index score. The EQ-5D index score has a range of 0 and 1 with 0 representing death and 1 representing perfect health. | The EQ-5D was administered at the beginning of the visit prior to seeing the investigator. Questionnaires were to be completed every 6 weeks (Day 1 of each cycle) for subsequent cycles and at the end of treatment visit. | 
| Health-related Quality of Life and Utility Values as Measured by EQ-5D - VAS | Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day. | The EQ-5D VAS was administered at the beginning of the visit prior to seeing the investigator. Questionnaires were to be completed every 6 weeks (Day 1 of each cycle) for subsequent cycles and at the end of treatment visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sorafenib (Nexavar), Erlotinib (Tarceva), First Line, HCC