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Completed

NCT Number: NCT00901901

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

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.

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Key information

Conditions

Carcinoma, Hepatocellular Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Randwick, New South Wales, Australia

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Sorafenib (Nexavar, BAY43-9006)

Drug

Sorafenib 400 mg twice daily

Erlotinib (Tarceva)

Drug

Erlotinib 150 mg once daily

Placebo

Drug

Matching erlotinib placebo 150 mg once daily

Primary outcomes

  1. Overall Survival

    Time frame: From randomization of the first patient until 34 months or date of death of any cause whichever came first

    Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.

Secondary outcomes

  1. Time to Radiological Tumor Progression (TTP)

    Time frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks

    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.

  2. Disease Control

    Time frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks

    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.

  3. Health-related Quality of Life and Utility Values as Measured by EQ-5D - Index

    Time frame: 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.

    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.

  4. Health-related Quality of Life and Utility Values as Measured by EQ-5D - VAS

    Time frame: 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.

    Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day.

Other outcomes

  1. Duration of Response

    Time frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks

    Duration of response - RECIST: number of days from the date that CR or PR is first documented to date that PD is first objectively documented or to death before progression. Note: the relevant date is that of the first documentation, not the confirmation date (if participant progressed or died then censored=no) or to last observation if participant did not progress or die then censored=yes note: this last observation date should be the same as that used for time to progression.

  2. Time to Response

    Time frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks

    Time to response was the number of days from randomization to the date the CR or PR was documented (with confirmation) (Note: the relevant date is that of the first documentation, not the confirmation date).

  3. Tumor Response

    Time frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks

    Tumor response was the proportion of participants with the best tumor response (ie, achieving either a confirmed complete response [CR] or partial response [PR], according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria).

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study title

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)

Acronym: SEARCH

Important dates

Study start
2009
Primary completion
2012
Study completion
2018
First posted
May 14, 2009
Registry last updated
May 30, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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