Evaluation of the combination of Nexavar and Tarceva for the treatment of liver cancer.

• Register: EUCTR
• Last refreshed on: 27 August 2018
• Main ID: EUCTR2008-006021-14-BE
• Date of registration: 13/05/2009
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG, 51368 Leverkusen, Germany
• Public title: Evaluation of the combination of Nexavar and Tarceva for the treatment of liver cancer.
• Scientific 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) - SEARCH
• Date of first enrolment: 26/06/2009
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006021-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, France, Germany, Greece, Hong Kong, Israel, Italy, Korea, Democratic People's Republic of, New Zealand, Peru, Poland, Russian Federation, Singapore, South Africa, Spain, Taiwan, United Kingdom, United States

Contacts

• Affiliation: Bayer HealthCare AG

• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Patients with histological or cytologically documented HCC or clinical diagnosis by AASLD criteria in cirrhotic subjects is required. For subjects without cirrhosis histological or cytological confirmation is necessary.

• Patients must have at least one tumor lesions that meets both of the following criteria:
- Lesion can be accurately measured in at least one dimension according to RECIST
- Lesion has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation

• Patients who have received local therapy are eligible. Local theapy must be completed at least 4 weeks prior to the baseline scan. Previously treated lesions will not be selected as target lesions.

• Patients with an ECOG PS of 0 or 1.

• Cirrhotic status of Child-Pugh Class A.

• Following Laboratory Parameters (as assessed by Central Laboratory):
- Platelet count = 60 x 109/L
- Hemoglobin = to 8.5 g/dl
- Total Bilirubin = 2.8 mg/dl
- ALT and AST = 5 x ULN
- Serum Creatinine = 1.5 x ULN
- PT international normalized ration (INR) = 2.3 or PT = 6 seconds above control
- Patients who are being therapeutically anticoagulated with an agent such as wafarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists and these patients have a Child-Pugh score = 6 during screening.

• Patients must provide written informed consent prior to any study procedures being performed

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Renal failure requiring hemo- or peritoneal dialysis

• Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) – related illness or serious acute or chronic illness.

• 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).

• Child-Pugh class B or C

• Previous treatment with yttrium- 90 spheres

• Clinically significant (i.e. symptomatic) peripheral vascular disease

• 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 defined as systolic blood pressure>150mmHg or diastolic blood pressure>90 mmHg despite optimal medical management. Myocardial infarction more than 6 months prior to study entry is permitted. (See Appendix 11.6)

• History of interstitial lung disease (ILD)

• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry

• Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0), except HBV/HCV infections

• Uncontrolled ascites (defined as not easily controlled with diuretic treatment)

• Pregnant or breast-feeding patients.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

To evaluate the clinical benefit of sorafenib 400 mg twice daily and erlotibib 150 mg once a day in subjects with unresectable advanced or metastatic Child-Pugh A HCC.
MedDRA version: 13.1 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 13.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: NEXAVAR
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sorafenib
CAS Number: 284461-73-0
Current Sponsor code: BAY 43-9006
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: TARCEVA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: erlotinib
CAS Number: 183321-74-6
Current Sponsor code: Ro-508231
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 25 mg-150 mg
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Overall Survival

Primary end point(s): Overall Survival measured via patient phone contacts after treatment is complete

Secondary Objective: Time to radiographic Tumor Progression (TTP)

Disease Control Rate (DCR)

Safety

Health Related Quality of Life (HRQoL) and utility values as measured by EQ-5D

Timepoint(s) of evaluation of this end point: From the date of randomization until the date of death due to any cause

Secondary Outcome(s)

Secondary end point(s): 1. Time to progression, response rate, duration of response, disease control rate, determined by tumor measurement using MRI or CT scans

2. Health-related quality of life and utility values as measured by the EQ-5D

3. Safety

Timepoint(s) of evaluation of this end point: 1. Every 6 weeks during treatment

2. Every 6 weeks during treatment

3. Every 3 weeks during treatment

Secondary ID(s)

BAY 43-9006/12917

2008-006021-14-DE