Trial record 1 of 1 for:    NCT00901901
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Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma (SEARCH)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00901901
First received: May 13, 2009
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Sorafenib (Nexavar, BAY43-9006) + Erlotinib, Tarceva
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization of the first patient until 34 months or date of death of any cause whichever came first ] [ Designated as safety issue: No ]
    Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Disease Control [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ] [ Designated as safety issue: No ]
    Disease control was defined as the number of participants who had a best response rating of complet 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.

  • 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. ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]
    Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day.


Other Outcome Measures:
  • Duration of Response [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to Response [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ] [ Designated as safety issue: No ]
    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).

  • Tumor Response [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 732
Study Start Date: May 2009
Estimated Study Completion Date: June 2014
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva)
Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd)
Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg twice daily + matching erlotinib placebo daily
Active Comparator: Sorafenib (Nexavar, BAY43-9006) + Placebo
Participants received sorafenib 400 mg twice daily (bid) and matching erlotinib placebo 150 mg tablet once daily (qd)
Drug: Sorafenib (Nexavar, BAY43-9006) + Erlotinib, Tarceva
Sorafenib 400 mg twice daily + erlotinib 150 mg daily

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00901901

  Show 163 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00901901     History of Changes
Other Study ID Numbers: 12917, 2008-006021-14
Study First Received: May 13, 2009
Results First Received: April 10, 2013
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration
Austrialia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Instituto de Salud Publica de Chile
China: Food and Drug Administration
Colombia: National Institutes of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Hong Kong: Department of Health
Israel: Ethics Commission
Italy: Ethics Committee
Japan: Pharmaceuticals and Medical Devices Agency
Peru: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan: Center for Drug Evaluation
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Bayer:
Sorafenib (Nexavar)
Erlotinib (Tarceva)
First Line
HCC

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Erlotinib
Sorafenib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014