Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma (SEARCH)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00901901 |
|
Recruitment Status :
Completed
First Posted : May 14, 2009
Results First Posted : September 30, 2013
Last Update Posted : May 30, 2019
|
Sponsor:
Bayer
Information provided by (Responsible Party):
Bayer
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Hepatocellular | Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Erlotinib (Tarceva) Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 732 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, 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) |
| Actual Study Start Date : | May 21, 2009 |
| Actual Primary Completion Date : | April 17, 2012 |
| Actual Study Completion Date : | May 23, 2018 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
|
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 Drug: Erlotinib (Tarceva) Erlotinib 150 mg once 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)
Sorafenib 400 mg twice daily Drug: Placebo Matching erlotinib placebo 150 mg once daily |
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 ]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 ]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 ]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.
- 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.
- 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 Outcome Measures:
- 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.
- 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).
- 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).
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00901901
Locations
Show 127 study locations
Sponsors and Collaborators
Bayer
Investigators
| Study Director: | Bayer Study Director | Bayer |
Additional Information:
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT00901901 |
| Other Study ID Numbers: |
12917 2008-006021-14 ( EudraCT Number ) |
| First Posted: | May 14, 2009 Key Record Dates |
| Results First Posted: | September 30, 2013 |
| Last Update Posted: | May 30, 2019 |
| Last Verified: | May 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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 Hydrochloride Sorafenib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |