Clinical Trials Register

Summary
EudraCT Number:	2008-006021-14
Sponsor's Protocol Code Number:	BAY43-9006/12917
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-04-20
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2008-006021-14

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

BAY43-9006/12917

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer AG
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer AG
B.5.2	Functional name of contact point	CTP Team / Ref:"EU CTR"/
B.5.3	Address:
B.5.3.1	Street Address	Bayer Schering Pharma AG S102, Level 2 Room 156
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayerhealthcare.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NEXAVAR
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer HealthCare AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/06/364
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	sorafenib
D.3.9.1	CAS number	284461-73-0
D.3.9.2	Current sponsor code	BAY 43-9006
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	TARCEVA
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	erlotinib
D.3.9.1	CAS number	183321-74-6
D.3.9.2	Current sponsor code	Ro-508231
D.3.9.3	Other descriptive name	erlotinib hydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	25 mg to 150 mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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.

E.1.1.1

Medical condition in easily understood language

Liver cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10019829
E.1.2	Term	Hepatocellular carcinoma recurrent
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10019828
E.1.2	Term	Hepatocellular carcinoma non-resectable
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Overall Survival

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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 ctyological 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

E.4

Principal 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 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. Myocardial infarction more than 6 months prior to study entry is permitted. (See Appendix 10.7)

• 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.

E.5 End points

E.5.1

Primary end point(s)

Overall Survival measured via patient phone contacts after treatment is complete

E.5.1.1

Timepoint(s) of evaluation of this end point

From the date of randomisation until the date of death due any cause

E.5.2

Secondary end point(s)

1. Time to progression, response rate, duration of response, disease control rate, determind by tumor measurment using MRI or CT scans
2. Health-related quality of life and utility values as measured by EQ-5D
3. Safety

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Information not present in EudraCT

E.6.2

Prophylaxis

Information not present in EudraCT

E.6.3

Therapy

Information not present in EudraCT

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Information not present in EudraCT

E.6.8

Bioequivalence

Information not present in EudraCT

E.6.9

Dose response

Information not present in EudraCT

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Information not present in EudraCT

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Information not present in EudraCT

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Information not present in EudraCT

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Information not present in EudraCT

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

Information not present in EudraCT

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Information not present in EudraCT

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last Visit of the last subjekt

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

385

F.4.2.2

In the whole clinical trial

700

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No plans for treatment different to expected normal treatment which ia at the discretion of their medical doctor

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-07-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-06-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-05-23

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